Gordo Posted July 20, 2016 Report Share Posted July 20, 2016 It's neat to see others with glucose metabolism issues benefiting from your encouragement to give CE a try. But I've been a bit underwhelmed by the Longecity community's response to the thread on CE you started. Really only you, me and Drew seem to have engaged on the thread... --Dean Agreed. I'm disappointed by LongeCity, but had low expectations going in. I'm still on the fence about whether I should update that thread or not? Part of me likes the idea of maintaining some sort of "summary" type thread that isn't 500 pages long like this one. Part of me also likes the idea of a "CE for dummies" type thread that I can send to people where they won't necessarily be overwhelmed (I'm not sure I can pull both off in a single thread though), even if there is little or no participation. One downside to LongeCity is that they only allow edits for a few hours after you post. I like how our version here allows edits for far longer (forever?). This would allow me for example to just stick all the "sciency" summary type updates in the first post only, and anyone not interested could easily skip that. I also like the idea of being able to fix mistakes after the fact any time they are noticed. Quote Link to comment Share on other sites More sharing options...
Gordo Posted July 20, 2016 Report Share Posted July 20, 2016 (edited) Neat glove-based cooling technology from Stanford. Not easy to reproduce though, with the vacuum it uses and all... Yea, apparently the Stamford ones originally cost $1800, but they have a slicker commercial product now for $895. It won't be long until the cheap Chinese knockoffs hit the market and you'll be able to get one for $30. I have thought about creating my own, it would be challenging but not impossible. Vacuum could come from a vacuum cleaner, you'd need some copper tubing (home depot) and a pump (fish tank supplies) to circulate water which could be pulled maybe just from a 5 gallon bucket of water + ice. I'd love to give this a try. It looks like these are taking the sports world by storm, see: Cold Chain technology at the World Cup ESPN's REVIEW of the above "coreControl" ($895) Edited July 20, 2016 by Gordo Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 21, 2016 Author Report Share Posted July 21, 2016 BAT and Cold Exposure Effects on Metabolic Rate and Glucose Metabolism in Healthy Men I thought this new study [1] and several studies it references (e.g. [2][3]) were interesting because of how meticulously they documented the quantitative impact of being BAT-positive on various aspects of metabolism. Each of these studies divided young healthy men into those who had detectable BAT (BAT+) vs. those who didn't (BAT-) based on PET imaging during cold exposure. Study [2] focused on calorie expediture. Mild cold exposure (19°C = 66 °F) increased the average calorie expenditure of BAT+ men by +410 kcal/d, vs only +42 kcal/d in the BAT- men. The men with the most BAT showed the biggest increase in cold-induced calorie expenditure as can be seen in the following figures: Study [1] found that among BAT+ men, diet-induced thermogenesis (the amount of heat produced after eating) was increased by about 60kcal/day on average - not all that much. The BAT+ men also burned more fat relative to carbohydrates (RQ of 0.86 vs. 0.89). Of course these were random healthy young men, probably not intentionally subjecting themselves to cold exposure to build BAT. Interestingly, while these guys weren't rail-thin, on average the BAT+ men were slightly skinnier than their BAT- counterparts. In [1], the BMI of BAT+ vs. BAT- men were 20.0 vs. 21.4 and in [2], BAT+ vs. BAT- BMIs were 21.2 vs. 22.6. So there is hope for us thin folks to develop BAT. I will note though that these guys were all in their 20s and the average age of BAT+ vs. BAT- men was 24 vs. 29, reinforcing the previous observation that BAT and BAT activity tends to go down with age. Study [3] was interesting, because it validated what many of us have observed - namely that BAT improves insulin sensitivity and glucose metabolism. They found the BAT+ men had less visceral fat and more subcutaneous fat than the BAT- group, which is a good thing, since visceral fat is more associated with inflammation and metabolic syndrome. Cold exposure increased the resting energy expenditure of the BAT+ men by 15% relative to the BAT- men, which would be about 225 kcal/day. But the really dramatic finding was in glucose disposal in response to cold exposure. Basically, they intravenously administered radioactive glucose to the men while they were in either thermoneutral vs. cold temperatures. As you can see from the graphs below, the BAT+ men showed large increases in their ability to clear glucose, as well as their insulin sensitivity during cold exposure: This suggests to me that cold exposure soon after eating may dramatically reduce glucose excursions of folks with BAT. --Dean --------- [1] Int J Obes (Lond). 2016 Jul 19. doi: 10.1038/ijo.2016.124. [Epub ahead of print] Brown adipose tissue is involved in diet-induced thermogenesis and whole-body fat utilization in healthy humans. Hibi M(1), Oishi S(1), Matsushita M(2), Yoneshiro T(3), Yamaguchi T(1), Usui C(4), Yasunaga K(1), Katsuragi Y(1), Kubota K(5), Tanaka S(4), Saito M(2). Free full text: http://dx.doi.org/10.1038/ijo.2016.124 BACKGROUND/OBJECTIVES: Brown adipose tissue (BAT) is a potential therapeutic target against obesity and diabetes through thermogenesis and substrate disposal with cold exposure. The role of BAT in energy metabolism under thermoneutral conditions, however, remains controversial. We assessed the contribution of BAT to energy expenditure (EE), particularly diet-induced thermogenesis (DIT), and substrate utilization in human adults. METHODS: In this cross-sectional study, BAT activity was evaluated in 21 men using (18)F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography ((18)F-FDG-PET/CT) after cold exposure (19 °C). The subjects were divided into BAT-positive (n=13) and BAT-negative (n=8) groups according to the (18)F-FDG-PET/CT findings. Twenty-four hour EE, DIT, and respiratory quotient were measured using a whole-room indirect calorimeter at 27 °C. RESULTS: Body composition, blood metabolites, and 24-h EE did not differ between groups. DIT (%), calculated as DIT divided by total energy intake, however, was significantly higher in the BAT-positive group (BAT-positive: 9.7±2.5%, BAT-negative: 6.5±4.0%, P=0.03). The 24-h respiratory quotient was significantly lower (P=0.03) in the BAT-positive group (0.860±0.028) than in the BAT-negative group (0.889±0.024). CONCLUSION: DIT and fat utilization were higher in BAT-positive subjects compared to BAT-negative subjects, suggesting that BAT has a physiologic role in energy metabolism.International Journal of Obesity accepted article preview online, 19 July 2016. doi:10.1038/ijo.2016.124. DOI: 10.1038/ijo.2016.124 PMID: 27430878 ---------- [2] Obesity (Silver Spring). 2011 Jan;19(1):13-6. doi: 10.1038/oby.2010.105. Epub 2010 May 6. Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Yoneshiro T(1), Aita S, Matsushita M, Kameya T, Nakada K, Kawai Y, Saito M. Author information: (1)Department of Nutrition, School of Nursing and Nutrition, Tenshi College, Sapporo, Japan. Brown adipose tissue (BAT) can be identified by (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in adult humans. Thirteen healthy male volunteers aged 20-28 years underwent FDG-PET after 2-h cold exposure at 19 °C with light-clothing and intermittently putting their legs on an ice block. When exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining seven showed no detectable uptake (BAT-negative group). The BMI and body fat content were similar in the two groups. Under warm conditions at 27 °C, the energy expenditure of the BAT-positive group estimated by indirect calorimetry was 1,446 ± 97 kcal/day, being comparable with that of the BAT-negative group (1,434 ± 246 kcal/day). After cold exposure, the energy expenditure increased markedly by 410 ± 293 (P < 0.05) and slightly by 42 ± 114 kcal/day (P = 0.37) in the BAT-positive and -negative groups, respectively. A positive correlation (P < 0.05) was found between the cold-induced rise in energy expenditure and the BAT activity quantified from FDG uptake. After cold exposure, the skin temperature in the supraclavicular region close to BAT deposits dropped by 0.14 °C in the BAT-positive group, whereas it dropped more markedly (P < 0.01) by 0.60 °C in the BAT-negative group. The skin temperature drop in other regions apart from BAT deposits was similar in the two groups. These results suggest that BAT is involved in cold-induced increases in whole-body energy expenditure, and, thereby, the control of body temperature and adiposity in adult humans. DOI: 10.1038/oby.2010.105 PMID: 20448535 ---------- [3] Diabetes. 2014 Dec;63(12):4089-99. doi: 10.2337/db14-0746. Epub 2014 Jul 23. Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans. Chondronikola M(1), Volpi E(2), Børsheim E(3), Porter C(3), Annamalai P(4), Enerbäck S(5), Lidell ME(5), Saraf MK(3), Labbe SM(6), Hurren NM(3), Yfanti C(7), Chao T(8), Andersen CR(3), Cesani F(9), Hawkins H(10), Sidossis LS(11). Free Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238005/ Abstract Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT(+) group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans. DOI: 10.2337/db14-0746 PMCID: PMC4238005 PMID: 25056438 Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 22, 2016 Author Report Share Posted July 22, 2016 Cool Fat Burner Knock-off - A $13 DIY Cooling Vest (Including Backup Ice Packs) As anyone reading this will know by now, I'm a big fan Cool Fat Burner (CFB) cooling vest(s). But now that it's summertime and hot here in Pittsburgh, and I'm going through all my CFB cool packs (12 of them) during the course of the day. Additional cold packs from CFB are not cheap - $50 for a pack of four. So I went looking online for alternatives, and boy did find a deal. Amazon sells these cold packs that are virtually identical to the "hardcore packs" sold by CFB. They are 6x10" and 24oz vs. the CFB packs which are 6x9" and 22oz. The extra 1" length is no problem, since the CFB pockets have plenty of extra room in that direction. And you can't beat the price - they are $13 for a set of 9 ($1.46 ea), vs. $50 + $10 tax & shipping for a set of 4 from CFB ($15 ea). That is less than 1/10th the price! So that's part one of a really inexpensive DIY cooling vest... Now the question is how to drape them to you body, without shelling out for the CFB vest, which cost $70 + shipping? Ever the engineer, here is a free cooling vest solution I came up with, made from an old long-sleeve shirt and some safety pins. Here is a picture of the pinned shirt, to create four pockets for the ice packs, just like the "classic" CFB vest has: You simply slip four frozen ice packs into the pockets through the shirt's neck hole, like this: Then put it on over you head putting your head through the hole created by the pinned sleeves, in order to wear the shirt over you shoulders like a cape. Here is what it looks like on: For anyone who wants to get fancy, you could sew along the lines of safety pins, and cut off the excess shirt material. But this way, I don't even ruin the shirt, in case the Steelers make it to the playoffs again this year (Go Steelers!). ☺ In short, with this DIY cooling vest and the Amazon ice packs (9x) above, you too can experiment with cold exposure for only $13. The equivalent from Cool Fat Burner would be $70 for the vest and four ice packs, plus another $50 for a second set of ice packs, or a total of $120. With tax and shipping the CFB equivalent comes to $141. So at $13, this DIY cooling vest solution is more than 90% off - Can't beat that! Let me know what you think, and if anyone else tries it. Happy chilling! --Dean P.S. For anyone wondering how I manage all those ice packs in my freezer, here is a rack I created for them out of some old corner freezer shelving to allow air circulation around the packs, and for easy transfer in/out of the freezer: Quote Link to comment Share on other sites More sharing options...
Gordo Posted July 23, 2016 Report Share Posted July 23, 2016 Great homemade vest, and that IS a killer deal from Amazon (great reviews there) can't believe they sell them so inexpensively. They are in my cart... I still plan to make a vacuum cooler just to see if it lives up to the hype (it seems quite gimicky to me). I'll need to figure out some way of objectively measuring its relative performance. Quote Link to comment Share on other sites More sharing options...
mikeccolella Posted July 23, 2016 Report Share Posted July 23, 2016 A swim or a cold shower would do the same thing right? Which brings up a ? I have had for some time.Dean, without pouncing on me please, I am wondering have you ever discussed the amount of time one needs to be exposed to cold to gain any benefits. I know you said it somewhere, but I really don't want to read all these posts to find it Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 23, 2016 Author Report Share Posted July 23, 2016 Mike, I am wondering have you ever discussed the amount of time one needs to be exposed to cold to gain any benefits. I know you said it somewhere, but I really don't want to read all these posts to find it Sorry Mike. I realize now that the last time you asked this question I interpreted it too narrowly, to mean what temperature does it take to activate BAT in someone who already has it. My answer was "the low 60s °F". What it takes to build BAT or beige adipose tissue is going to depend on a lot of things, including your heritage (Caucasian better than Asian or African), your genetics (best to be Being of genotype TT for rs1800592 and AA for rs4994 as reported by 23andMe), your gender (women better than men), your age (younger better than older) and your weight (not too fat or too thin - BMI in the low 20s appears best). But here I discussed a study [1] with some concrete numbers for building BAT via cold exposure. If found exposure to 17 °C (62.5 °F) for 2h/day for six weeks was enough to nearly triple the average cold-induced thermogenesis (~100 kcal/day → ~300 kcal/day) in healthy people who initially didn't have any BAT. Of the 8 initially BAT- men in the study, 6 of them (75%) showed detectable BAT activity by the end of six weeks of cold exposure. Interestingly, this new study from last month [2], instructed some men to expose themselves to cold for six weeks in late winter in Sweden for at least one hour per day, while others (controls) were told to avoid cold whenever possible. After six weeks, the controls (left graph below) had nearly identical BAT volume to when they started. In contrast, after throwing out the two non-compliant men (highlighted in yellow below right), the men who exposed themselves to cold for six weeks (avg 79min / day) showed a modest increase in BAT volume, as measured by cold-induced BAT activity using PET imaging. But the change in BAT activity was pretty modest. They saw a small decrease in metabolic rate of the warm controls (-50kcal/day), and a similar modest increase in metabolic rate of the cold-exposed group (+70kcal/day). This was true at both room temperature and in cold conditions. The self-administered and self-reported nature of the cold-exposure in this study makes it less definitive. Nevertheless, it suggests that one hour per day of "casual" cold exposure may be enough to cause a modest increase in BAT volume and BAT activity. However this mild amount of cold exposure wasn't sufficient to result in changes in metabolic parameters of the subjects - i.e. none of the usual positive metabolic effects of cold exposure were observed (reduced weight, lower fasting insulin, lower fasting glucose). So one hour of casual cold exposure per day probably isn't enough to have much of a positive effect. So "a couple hours per day of rigorous cold exposure for a few weeks" would be my answer to how much CE it probably takes to see positive results (e.g. improved glucose metabolism). --Dean ------------ [1] J Clin Invest. 2013 Aug;123(8):3404-8. doi: 10.1172/JCI67803. Epub 2013 Jul 15. Recruited brown adipose tissue as an antiobesity agent in humans. Yoneshiro T(1), Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, Iwanaga T, Saito M. Author information: (1)Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, Japan. yoneshiro@med.hokudai.ac.jp Free full text: http://www.ncbi.nlm....les/PMC3726164/ Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron emission tomography and computed tomography, we previously reported that BAT decreases with age and thereby accelerates age-related accumulation of body fat in humans. Thus, the recruitment of BAT may be effective for body fat reduction. In this study, we examined the effects of repeated stimulation by cold and capsinoids (nonpungent capsaicin analogs) in healthy human subjects with low BAT activity. Acute cold exposure at 19°C for 2 hours increased energy expenditure (EE). Cold-induced increments of EE (CIT) strongly correlated with BAT activity independently of age and fat-free mass. Daily 2-hour cold exposure at 17°C for 6 weeks resulted in a parallel increase in BAT activity and CIT and a concomitant decrease in body fat mass. Changes in BAT activity and body fat mass were negatively correlated. Similarly, daily ingestion of capsinoids for 6 weeks increased CIT. These results demonstrate that human BAT can be recruited even in individuals with decreased BAT activity, thereby contributing to body fat reduction. PMCID: PMC3726164 PMID: 23867622 --------- [2] Metabolism. 2016 Jun;65(6):926-34. doi: 10.1016/j.metabol.2016.03.012. Epub 2016 Apr 1. A randomized trial of cold-exposure on energy expenditure and supraclavicular brown adipose tissue volume in humans. Romu T(1), Vavruch C(2), Dahlqvist-Leinhard O(3), Tallberg J(3), Dahlström N(3), Persson A(3), Heglind M(4), Lidell ME(4), Enerbäck S(4), Borga M(1), Nystrom FH(5). Author information: (1)Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; Department of Biomedical Engineering, Linköping University, Linköping, Sweden. (2)Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University. (3)Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. (4)Department of Medical and Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. (5)Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University. Electronic address: fredrik.h.nystrom@liu.se. Free full text: http://www.metabolismjournal.com/article/S0026-0495(16)30002-6/fulltext OBJECTIVE: To study if repeated cold-exposure increases metabolic rate and/or brown adipose tissue (BAT) volume in humans when compared with avoiding to freeze. DESIGN: Randomized, open, parallel-group trial. METHODS: Healthy non-selected participants were randomized to achieve cold-exposure 1hour/day, or to avoid any sense of feeling cold, for 6weeks. Metabolic rate (MR) was measured by indirect calorimetry before and after acute cold-exposure with cold vests and ingestion of cold water. The BAT volumes in the supraclavicular region were measured with magnetic resonance imaging (MRI). RESULTS: Twenty-eight participants were recruited, 12 were allocated to controls and 16 to cold-exposure. Two participants in the cold group dropped out and one was excluded. Both the non-stimulated and the cold-stimulated MR were lowered within the group randomized to avoid cold (MR at room temperature from 1841±199 kCal/24h to 1795±213 kCal/24h, p=0.047 cold-activated MR from 1900±150 kCal/24h to 1793±215 kCal/24h, p=0.028). There was a trend towards increased MR at room temperature following the intervention in the cold-group (p=0.052). The difference between MR changes by the interventions between groups was statistically significant (p=0.008 at room temperature, p=0.032 after cold-activation). In an on-treatment analysis after exclusion of two participants that reported ≥8days without cold-exposure, supraclavicular BAT volume had increased in the cold-exposure group (from 0.0175±0.015l to 0.0216±0.014l, p=0.049). CONCLUSIONS: We found evidence for plasticity in metabolic rate by avoiding to freeze compared with cold-exposure in a randomized setting in non-selected humans. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.metabol.2016.03.012 PMID: 27173471 Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 23, 2016 Author Report Share Posted July 23, 2016 All, Back in early July in a post flippantly titled Luigi Fontana - Missing the Obvious? I reviewed a new paper [1] by Luigi and colleagues about branch chain amino acid (BCAA) restriction, and especially Leucine restriction. What they found was summarized in the graphical abstract: The authors weren't sure what the molecular pathway was that resulted in the metabolic benefits (reduced weight and improve insulin sensitivity without eating less or being more physically active): [T]he ultimate molecular mechanism that drives the effect of a leucine reduced diet on white adipose tissue is as yet unknown. I speculated that it was likely an effect of the browning of white fat, based especially on another study on Leucine restriction (PMID 26643647 discussed here), that saw similar effects and traced it to increased UCP1 expression (i.e. browning) in white fat. I sent an email to Luigi, inquiring if he'd considered this explanation, saying: ... Take a look at that post for more discussion of why it seems to me that BAT/beige fat thermogenesis is the likely explanation for your apparent mystery. I'd love to know what you think, and if I can post your response to the CR forums. I thought he'd forgot or blew me off, but today he got back to me. Here is what he said: Dear Dean, Nice to hear from you. Yes, we think that most likely this is the cause. Animals were kept in metabolic cages and we found that physical activity was not increased and food consumption was not decreased. So, most likely there is BCAA induced uncoupling. Yours, Lu So now we have it directly from luigi - Amino acid / BCAA / Leucine restriction probably improves metabolic healthy by turning white fat to brown. --Dean -------------------- [1] Cell Rep. 2016 Jun 21. pii: S2211-1247(16)30733-1. doi: 10.1016/j.celrep.2016.05.092. [Epub ahead of print] Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health. Fontana L(1), Cummings NE(2), Arriola Apelo SI(3), Neuman JC(4), Kasza I(5), Schmidt BA(3), Cava E(6), Spelta F(7), Tosti V(7), Syed FA(3), Baar EL(3), Veronese N(8), Cottrell SE(9), Fenske RJ(4), Bertozzi B(10), Brar HK(3), Pietka T(10), Bullock AD(11), Figenshau RS(11), Andriole GL(11), Merrins MJ(12), Alexander CM(5), Kimple ME(13), Lamming DW(14). Free full text: http://linkinghub.el...1247(16)30733-1 Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet. Copyright © 2016. Published by Elsevier Inc. DOI: 10.1016/j.celrep.2016.05.092 PMID: 27346343 Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted July 23, 2016 Report Share Posted July 23, 2016 MR gets furious when he reads a post where someone claims "restriction" of any individual amino-acid. I don't think he'll like it if you make any claims about restricting BCAAs or leucine. How was such restriction achieved in humans according to PMID:27346343? According to the supplemental material: "Human PR Diet - Each participant randomized to the PR diet was fed costumized isocaloric PR diets prepared by the Metabolic kitchen of the Washington University CARS." Not super helpful. Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 23, 2016 Author Report Share Posted July 23, 2016 TomB, MR gets furious when he reads a post where someone claims "restriction" of any individual amino-acid. I don't think he'll like it if you make any claims about restricting BCAAs or leucine. Oooh. Michael might not like it. Now I'm in trouble. I dare him to say something, particularly since it wasn't me but Luigi who talked about BCAA and leucine restriction, e.g. in the paper highlights: Protein-restricted (PR) and branched-chain amino acid (BCAA)-restricted diets improve metabolic health On second thought, I hope Michael doesn't respond. Instead I'd really like him to read and analyze the new paper on the crazy metabolic impact of sucralose (and likely other artificial sweeteners) discussed here. But you are right Tom, it would be interesting to know what modifications the folks in the WUSTL kitchen did to the diet of their human subjects to make it low in BCAAs and leucine. --Dean Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 23, 2016 Author Report Share Posted July 23, 2016 More Evidence Resveratrol Improves Insulin Sensitivity Through BAT Activation Back in this post, I first pointed to evidence that resveratrol causes the browning of white fat (PMID: 25761413). This new study [1] published last month further confirms this association. They studied rat adipose tissue both in vitro and in vivo and found that: Culturing fat cells in a medium supplemented with resveratrol increased UCP1 expression Feeding mice resveratrol, either while eating standard chow or a high-fat diet, resulted in significant (p < 0.05) increases in the number of brown(ish) adipocytes and BAT weight. Feeding mice resveratrol along with a high-fat diet more than doubled UPC1 expression (and AMPK expression) in fat cells, but the same boost in UCP1 expression from or resveratrol was not observed in rats fed normal chow. Insulin sensitivity was improved with resveratrol feeding in both diet groups. So this looks like confirmation that resveratrol boost brown fat and brown fat activity, particularly in the context of a diet with lots of fat. --Dean ------- [1] Endocrinol Metab (Seoul). 2016 Jun;31(2):328-35. doi: 10.3803/EnM.2016.31.2.328. Epub 2016 Apr 8. The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes. Ku CR(1), Cho YH(1), Hong ZY(2), Lee H(1), Lee SJ(1), Hong SS(1), Lee EJ(3). Free full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923418/ BACKGROUND: Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes. METHODS: For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV. RSV was provided via oral gavage once daily during the in vivo experiments. RESULTS: RSV treatment of primary cultured brown preadipocytes promoted mitochondrial activity, along with over-expression of estrogen receptor α (ER-α). In OLETF rats, both HFD and RSV treatment increased the weight of BAT and the differentiation of BAT. However, only RSV increased the mitochondrial activity and ER-α expression of BAT in the HFD-fed group. Finally, RSV improved the insulin sensitivity of OLETF rats by increasing the mitochondrial activity of BAT, despite having no effects on white adipocytes and muscles in either diet group. CONCLUSION: RSV could improve insulin resistance, which might be associated with mitochondrial activity of brown adipocyte. Further studies evaluating the activity of RSV for both the differentiation and mitochondrial activity of BAT could be helpful in investigating the effects of RSV on metabolic parameters. DOI: 10.3803/EnM.2016.31.2.328 PMCID: PMC4923418 PMID: 27077216 Quote Link to comment Share on other sites More sharing options...
mikeccolella Posted July 24, 2016 Report Share Posted July 24, 2016 Dean wrote: But here I discussed a study [1] with some concrete numbers for building BAT via cold exposure. If found exposure to 17 °C (62.5 °F) for 2h/day for six weeks was enough to nearly triple the average cold-induced thermogenesis (~100 kcal/day → ~300 kcal/day) in healthy people who initially didn't have any BAT. Of the 8 initially BAT- men in the study, 6 of them (75%) showed detectable BAT activity by the end of six weeks of cold exposure. Thanks Dean. That is the kind of practical information I was looking for. I am so pleased because that sounds like a cinch. 2 hours a day at 60ish degrees. Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 24, 2016 Author Report Share Posted July 24, 2016 New Support for CR / CE Synergy Model Michael has been understandably skeptical of the model of CR / CE synergy I proposed here and discussed further here. This model can be summarized in the rather complicated diagram below. Notice the yellow highlights? These represent aspects of the model that are supported by three papers [1][2][3] published in the last month: Study [1] address the significance of SIRT1 for BAT activity. It found that mice genetically deficient in SIRT1 (SIRT1(+ /-)) expressed less SIRT1 in BAT tissue, and this deficit was accompanied by a decrease in mitochondrial DNA expression, reduced expression of UPC1, as well as a decrease in whole body oxygen consumption and an inability for the mice to keep warm during a cold challenge. In short, [1] suggests that SIRT1 is critical for maintaining proper function of BAT, by boosting mitochondria and UPC1 expression. Study [2] looked at the importance of Protein Kinase A (PKA) for promoting BAT activity. Mice genetically programmed to overexpress PKA in adipose tissue were protected from getting obese on a high fat diet, and exhibited increased insulin sensitivity, glucose tolerance and pancreatic β-cell function - a topic many of us are concerned about as a result of the tendency of serious CR to impair glucose tolerance. They also expended more energy without eating more or being more physically active. The mechanism? - you guessed it, increased expression of UCP1 in subcutaneous WAT and BAT, and therefore increased thermogenesis. In support of the above model, the authors conclude: These data show that PKA activation is sufficient to induce changes to a brown-like phenotype in the subcutaneous WAT and to increase UCP1 expression in BAT. The authors aren't sure how PKA increases the browning of WAT or increases BAT activity, saying: Overall, although these studies alter adipose PKA activity, they do not establish the functional effects of PKA activity. The importance of our data is that it shows that activation of PKA alone in adipose tissue is sufficient to induce resistance to diet-induced obesity. but there is good evidence that PKA is a mTOR regulator, and that mTOR is critical in the BAT synthesis and the browning of white fat, as we discussed here based on [4], which linked increased epinephrine (which is upregulated by cold) to elevated PKA activity in adipose tissue, which acted through mTOR1 (specifically the RAPTOR complex) to brown adipose tissue, independent of the insulin/AKT signalling pathway, exactly as shown in the diagram above. Study [3] lends further support to the important role mTOR plays in WAT and BAT synthesis, and in insulin sensitivity. Mice that lacked mTOR in adipose tissue had decreased BAT and WAT mass, and were insulin resistant. They conclude: Our study reveals the critical role of the mTOR signalling pathway in regulating adipose tissues development, whole-body energy metabolism and insulin sensitivity. CR reduces insulin and IGF-1 signalling, which may have several good effects wrt inflammation and aging. But it also knocks down the anabolic action of mTOR, which can result in metabolic dysfunction (and impaired glucose tolerance in some of us), and reduced bone and muscle mass. These papers support the idea that cold exposure can overcome these negative effects of CR by activity mTOR via a separate pathway from insulin/IGF-1, involving PKA. --Dean ------------ [1] Zhonghua Yi Xue Za Zhi. 2016 Jun 21;96(23):1859-62. doi: 10.3760/cma.j.issn.0376-2491.2016.23.017. [Effect of SIRT1 deficiency on function of brown adipose tissue in obese mice]. [Article in Chinese] Zheng XB(1), Ai HY, Yuan SH, Cao HY, Liang H, Weng JP, Xu F. Author information: (1)Department of Endocrinology and Metabolism, Third Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Diabetology of Guangdong Province, Guangzhou 510630, China. Free full text: http://zhyxzz.yiigle.com/CN112137201623/897269.htm?locale=zh_CN OBJECTIVE: To investigate the effect of silent mating type information regulation 2 homolog 1 (SIRT1) deficiency on function of brown adipose tissue (BAT) in high-fat diet (HFD)-induced obese mice. METHODS: Male SIRT1 deficient heterozygous (SIRT1(+ /-)) mice and their wild-type (WT) littermates were challenged with a HFD diet for 16 weeks to induce obesity model.Energy metabolic cages were used to measure oxygen consumption and heat production, and cold tolerance test was to evaluate the adaptive thermogenic function.With brown fat collected after the diet intervention, determination techniques were adopted included HE staining for morphologic changes, immunohistochemical staining and Western blotting for uncoupling protein 1 (UCP1) expression, quantitative real-time PCR for relative content of mitochondria DNA (mtDNA). RESULTS: Compared to WT controls, SIRT1(+ /-) mice displayed significant decreases in both oxygen consumption and heat production[(2 681±297) vs (3 017±313) ml·kg(-1)·h(-1,) (19.05±2.40) vs (21.15±2.49) kcal·kg(-1)·h(-1,) both P<0.05)], as well as an impairment in maintaining their body temperature during the cold challenge.HE staining revealed the accumulation of larger lipid droplets in BAT of SIRT1(+ /-) mice, and both immunohistochemical staining and Western blotting indicated an obvious reduction in expression of UCP1 (P<0.05). Quantitative real-time PCR showed a significant decrease in the relative mtDNA content in BAT of SIRT1(+ /-) mice (0.38±0.10 vs 1.00±0.40, P<0.05). CONCLUSION: SIRT1 deficiency promotes BAT dysfunction, meaning that whitening in obese mice. PMID: 27356800 ----------- [2] Am J Physiol Regul Integr Comp Physiol. 2016 Jul 1;311(1):R79-88. doi: 10.1152/ajpregu.00114.2016. Epub 2016 Apr 20. Protein kinase A induces UCP1 expression in specific adipose depots to increase energy expenditure and improve metabolic health. Dickson LM(1), Gandhi S(1), Layden BT(2), Cohen RN(1), Wicksteed B(3). Author information: (1)Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, The University of Chicago, Chicago, Illinois; (2)Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois. (3)Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, The University of Chicago, Chicago, Illinois; Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and barton.wicksteed@northwestern.edu. Adipose tissue PKA has roles in adipogenesis, lipolysis, and mitochondrial function. PKA transduces the cAMP signal downstream of G protein-coupled receptors, which are being explored for therapeutic manipulation to reduce obesity and improve metabolic health. This study aimed to determine the overall physiological consequences of PKA activation in adipose tissue. Mice expressing an activated PKA catalytic subunit in adipose tissue (Adipoq-caPKA mice) showed increased PKA activity in subcutaneous, epididymal, and mesenteric white adipose tissue (WAT) depots and brown adipose tissue (BAT) compared with controls. Adipoq-caPKA mice weaned onto a high-fat diet (HFD) or switched to the HFD at 26 wk of age were protected from diet-induced weight gain. Metabolic health was improved, with enhanced insulin sensitivity, glucose tolerance, and β-cell function. Adipose tissue health was improved, with smaller adipocyte size and reduced macrophage engulfment of adipocytes. Using metabolic cages, we found that Adipoq-caPKA mice were shown to have increased energy expenditure, but no difference to littermate controls in physical activity or food consumption. Immunoblotting of adipose tissue showed increased expression of uncoupling protein-1 (UCP1) in BAT and dramatic UCP1 induction in subcutaneous WAT, but no induction in the visceral depots. Feeding a HFD increased PKA activity in epididymal WAT of wild-type mice compared with chow, but did not change PKA activity in subcutaneous WAT or BAT. This was associated with changes in PKA regulatory subunit expression. This study shows that adipose tissue PKA activity is sufficient to increase energy expenditure and indicates that PKA is a beneficial target in metabolic health. DOI: 10.1152/ajpregu.00114.2016 PMID: 27097660 ----------- [3] Diabetologia. 2016 Jun 13. [Epub ahead of print] Adipocyte-specific deletion of mTOR inhibits adipose tissue development and causes insulin resistance in mice. Shan T1,2, Zhang P3,4, Jiang Q3,5, Xiong Y3, Wang Y6, Kuang S7,8. Abstract AIMS/HYPOTHESIS: The in vivo role of mechanistic target of rapamycin (mTOR) in the development and function of adipose tissue, especially brown adipose tissue (BAT), is not well understood. Here, we aimed to assess the effect of mTOR (also known as Mtor) knockout on adipose tissues and systemic energy metabolism. METHODS: We generated adipocyte-specific mTOR-knockout mice (Adipoq-mTOR) by crossing adiponectin-Cre (Adipoq-Cre) mice with mTOR flox/flox mice. The mice were then subjected to morphological, physiological (indirect calorimetry, glucose and insulin tolerance tests) and gene expression analyses to determine the role of mTOR in adipose tissues. RESULTS: We provide in vivo evidence that mTOR is essential for adipose tissue development and growth. Deletion of mTOR decreased the mass of both BAT and white adipose tissues (WAT) and induced browning of WAT. In addition, ablation of mTOR in adipose tissues caused insulin resistance and fatty liver in the Adipoq-mTOR mice. Furthermore, mTOR was required for adipocyte differentiation in vivo and activation of PPARγ ameliorated the differentiation deficiency of the mTOR-null adipocytes. CONCLUSIONS/INTERPRETATION: Our findings demonstrate that mTOR is a critical regulator of adipogenesis and systemic energy metabolism. Our study provides key insights into the role of mTOR in adipose tissues; such knowledge may facilitate the development of novel strategies with which to treat obesity and related metabolic diseases. KEYWORDS: Adipose; Browning; Insulin resistance; PPARγ; mTOR PMID: 27294611 DOI: 10.1007/s00125-016-4006-4 --------- [4] J Clin Invest. 2016 Mar 28. pii: 83532. doi: 10.1172/JCI83532. [Epub ahead of print] Activation of mTORC1 is essential for β-adrenergic stimulation of adipose browning. Liu D, Bordicchia M, Zhang C, Fang H, Wei W, Li JL, Guilherme A, Guntur K, Czech MP, Collins S. Free full text: https://www.jci.org/.../view/83532#B79 A classic metabolic concept posits that insulin promotes energy storage and adipose expansion, while catecholamines stimulate release of adipose energy stores by hydrolysis of triglycerides through β-adrenergic receptor (βARs) and protein kinase A (PKA) signaling. Here, we have shown that a key hub in the insulin signaling pathway, activation of p70 ribosomal S6 kinase (S6K1) through mTORC1, is also triggered by PKA activation in both mouse and human adipocytes. Mice with mTORC1 impairment, either through adipocyte-specific deletion of Raptor or pharmacologic rapamycin treatment, were refractory to the well-known βAR-dependent increase of uncoupling protein UCP1 expression and expansion of beige/brite adipocytes (so-called browning) in white adipose tissue (WAT). Mechanistically, PKA directly phosphorylated mTOR and RAPTOR on unique serine residues, an effect that was independent of insulin/AKT signaling. Abrogation of the PKA site within RAPTOR disrupted βAR/mTORC1 activation of S6K1 without affecting mTORC1 activation by insulin. Conversely, a phosphomimetic RAPTOR augmented S6K1 activity. Together, these studies reveal a signaling pathway from βARs and PKA through mTORC1 that is required for adipose browning by catecholamines and provides potential therapeutic strategies to enhance energy expenditure and combat metabolic disease. PMID: 27018708 Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted July 25, 2016 Report Share Posted July 25, 2016 Dean if this is not the right thread, feel free to remove this post. Admittedly, not fully on topic, but interesting: You Turn Me Cold: Evidence for Temperature Contagion Abstract IntroductionDuring social interactions, our own physiological responses influence those of others. Synchronization of physiological (and behavioural) responses can facilitate emotional understanding and group coherence through inter-subjectivity. Here we investigate if observing cues indicating a change in another's body temperature results in a corresponding temperature change in the observer. MethodsThirty-six healthy participants (age; 22.9±3.1 yrs) each observed, then rated, eight purpose-made videos (3 min duration) that depicted actors with either their right or left hand in visibly warm (warm videos) or cold water (cold videos). Four control videos with the actors' hand in front of the water were also shown. Temperature of participant observers' right and left hands was concurrently measured using a thermistor within a Wheatstone bridge with a theoretical temperature sensitivity of <0.0001°C. Temperature data were analysed in a repeated measures ANOVA (temperature × actor's hand × observer's hand). ResultsParticipants rated the videos showing hands immersed in cold water as being significantly cooler than hands immersed in warm water, F(1,34) = 256.67, p<0.001. Participants' own hands also showed a significant temperature-dependent effect: hands were significantly colder when observing cold vs. warm videos F(1,34) = 13.83, p = 0.001 with post-hoc t-test demonstrating a significant reduction in participants' own left (t(35) = −3.54, p = 0.001) and right (t(35) = −2.33, p = 0.026) hand temperature during observation of cold videos but no change to warm videos (p>0.1). There was however no evidence of left-right mirroring of these temperature effects p>0.1). Sensitivity to temperature contagion was also predicted by inter-individual differences in self-report empathy. ConclusionsWe illustrate physiological contagion of temperature in healthy individuals, suggesting that empathetic understanding for primary low-level physiological challenges (as well as more complex emotions) are grounded in somatic simulation. Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 25, 2016 Author Report Share Posted July 25, 2016 Tom, That temperature contagion paper is interesting. I looked into the details of the full text, and it appears that on average subjects watching a video of someone plunging one hand into an ice bath triggered about a 0.2 °C (0.36 °F) decrease in the skin temperature of the corresponding hand. The more empathetic your personality, the larger the change in skin temperature. Not a huge effect, but as you say, quite interesting. Vicarious cold exposure! --Dean Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 25, 2016 Author Report Share Posted July 25, 2016 Exercise Browns the Fat inside Muscle Cells to Prevent Insulin Resistance We've recently been discussing insulin resistance and glucose intolerance a lot (here and here), and how exercise and cold exposure can alleviate the problem of impaired glucose tolerance that some folks on severe CR have experienced. One hypothesis for how glucose metabolism might be impaired in CR folks is that lack of muscle mass and lack of (brown) adipose tissue in severely CRed folks could leave no place for the glucose to go after a meal, so it remains in circulation, doing damage. Another hypothesis for glucose intolerance in general (not just in CR folks) is the so called "intramyocellular lipid" hypothesis, promoted most vocally by Dr. Neal Barnard, in fact just last week in this short video (warning: Facebook link). But after looking into it a while back, I became somewhat skeptical of Dr. Barnard's explanation, at least in it's simplest form - that is, lipids inside muscle cells "gum up" the pathway by which glucose is transported from the blood into muscle cells to be burned as fuel. This review in particular [2] does a good job pointing out that the connection between intramyocellular lipids and insulin resistance is a lot more complicated than originally thought, and pointing out that lipid drops inside muscle cells serve important metabolic functions, foreshadowing this new paper [1] I'm highlighting today. But before we get to [1], it's important to point out one apparent weakness of the "muscle lipid → insulin resistance" hypothesis. That is the fact that endurance athletes, who have very good insulin sensitivity, nevertheless have been shown to have elevated amounts of lipid droplets in their muscle cells, nearly as much as obese folks and diabetics in fact, a phenomenon referred to as the athlete’s paradox [3]. The authors of [3] summarized their findings (in 2001) as such: In summary, skeletal muscle of trained endurance athletes is markedly insulin sensitive andhas a high oxidative capacity, despite having an elevated lipid content. Inconclusion, the capacity for lipid oxidation may be an important mediator of theassociation between excess muscle lipid accumulation and insulin resistance. With that foreshadowing, I bet you can guess what today's paper [1] found. Yup, exercise turns the fat inside muscles to brown, making it metabolically active and able to burn more, rather than less, glucose. In the paper, they used female C57BL/6 mice and (presumably) housed them at standard, chilly-for-mice lab temperature. They fed them either a standard or high-fat diet ad lib, and gave half of each group a running wheel for six hours per night. They ran two experiments with a group of mice that got the running wheel from the start for six weeks, or were fed the HFD for 12 weeks before being given the running wheel for an additional six weeks. The mice with the running wheel worked their little butts off as mice are prone to do when given a wheel, running an average of about 6 miles (10 km) per night! Given their size, that's a heck of a lot of endurance exercise! In the high fat group, running prevented most of the diet-induced weight & fat mass gain. Interestingly, running did not increase muscle mass in the high fat exercise group relative to the high fat sedentary controls. Not surprisingly, the high fat diet increased lipids inside muscles in both the exercise and sedentary groups relative to the mice fed a standard, low-fat chow. Here is the all-important data showing lipid (triglyceride) content in muscle cells of the control (low-fat) diet mice (CTL), control diet + exercise mice (CTL-E), high fat diet mice (HFD), and high fat diet + exercise mice (HFD-E): As you can see, in both sets of experiments, the muscles of the exercise mice showed a trend towards more fat in their muscles than the sedentary mice - recapitulating the athlete's paradox in mice. The difference was especially dramatic in the high fat diet mice (HFD vs. HFD-E). Unfortunately, they didn't measure insulin sensitivity, but it's virtually certain that the exercise mice were more insulin sensitive than the sedentary controls, based on previous data in humans and mice of the effects of exercise on insulin sensitivity. What they did measure were the mRNA level of proteins that are markers for brown adipose tissue inside the muscle cells of the various groups. Sure enough, UCP1 and the mitochondria-biogenesis-promoting PGC1α were dramatically elevated in the mice that exercised. In fact, UCP1 mRNA was increased by a factor of 100 - 200 in the experiment where access to the running wheel was delayed until the mice got pretty chubby (right graph below): In short, the fat in the muscles of exercising mice was a lot "browner", meaning it augmented rather than impaired the ability of muscles to burn glucose, and hence serves to explain the athlete's paradox. Most interesting of all to me was this statement the concluding paragraph of the paper (my emphasis): Additionally, HFD was additive to exercise in browning muscle lipid and, thus, exogenous lipid consumption may be a critical factor in the phenotypic shifts that occur with endurance training. This mouse model suggests that increased muscle lipid may represent a potential beige fat depot that serves the metabolic needs of exercise. In other words, in order to benefit from insulin-sensitizing effects of endurance exercise, it looks like you may need to eat extra calories, and especially extra fat, in order to build up calorie-burning beige fat deposits in muscles. It is no wonder therefore that rail-thin CR folks with very little skeletal muscle (and virtually no fat or brown fat), exhibit impaired glucose tolerance. Just as I've speculated elsewhere (here too), this study seems to confirm that they likely have too little muscle and fat to serve as sinks for the circulating glucose. This also goes a long way towards explaining why exercise improves insulin sensitivity in obese and diabetic people, even without calorie restriction and without/before weight loss [4][5][6]. In a backhanded sort of way quite the opposite of what he intended, Michael is right. Health and longevity is not about the weight. But it's also not about the absolute number of calories either. Gordo, still think the combination of cold exposure and endurance exercise is a counterproductive waste of time and energy? Finally, these results make Michael's quip a while back about jiggling pecs as the explanation for thermogenesis and as a way to dismiss the benefits of cold exposure and exercise look even sillier... To quote my least favorite politician - "so sad." --Dean ----------- [1] Front Endocrinol (Lausanne). 2016 Jun 30;7:80. doi: 10.3389/fendo.2016.00080. eCollection 2016. Exercise Increases and Browns Muscle Lipid in High-Fat Diet-Fed Mice. Morton TL(1), Galior K(1), McGrath C(1), Wu X(1), Uzer G(1), Uzer GB(1), Sen B(1), Xie Z(1), Tyson D(1), Rubin J(1), Styner M(1). Author information: (1)Department of Medicine, Division of Endocrinology and Metabolism, University of North Carolina at Chapel Hill , Chapel Hill, NC , USA. Free full text: http://journal.frontiersin.org/article/10.3389/fendo.2016.00080/full Muscle lipid increases with high-fat feeding and diabetes. In trained athletes, increased muscle lipid is not associated with insulin resistance, a phenomenon known as the athlete's paradox. To understand if exercise altered the phenotype of muscle lipid, female C57BL/6 mice fed CTL or high-fat diet (HFD for 6 or 18 weeks) were further divided into sedentary or exercising groups (CTL-E or HFD-E) with voluntary access to running wheels for the last 6 weeks of experiments, running 6 h/night. Diet did not affect running time or distance. HFD mice weighed more than CTL after 18 weeks (p < 0.01). Quadriceps muscle TG was increased in running animals and in sedentary mice fed HFD for 18 weeks (p < 0.05). In exercised animals, markers of fat, Plin1, aP2, FSP27, and Fasn, were increased significantly in HFD groups. Ucp1 and Pgc1a, markers for brown fat, increased with exercise in the setting of high fat feeding. Fndc5, which encodes irisin, and CytC were sensitive to exercise regardless of diet. Plin5 was increased with HFD and unaffected by exercise; the respiratory exchange ratio was 15% lower in the 18-week HFD group compared with CTL (p < 0.001) and 10% lower in 18 weeks HFD-E compared with CTL-E (p < 0.001). Increased Ucp1 and Pgc1a in exercised muscle of running mice suggests that a beige/brown fat phenotype develops, which differs from the fat phenotype that induces insulin resistance in high fat feeding. This suggests that increased muscle lipid may develop a "brown" phenotype in the setting of endurance exercise training, a shift that is further promoted by HFD. DOI: 10.3389/fendo.2016.00080 PMID: 27445983 --------- [2] Diabetologia. 2012 Oct;55(10):2551-4. doi: 10.1007/s00125-012-2597-y. Epub 2012 Jun 3. Revisiting the connection between intramyocellular lipids and insulin resistance: a long and winding road. Muoio DM(1). Author information: (1)Sarah W Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA. muoio@duke.edu Full text: http://link.springer.com/article/10.1007/s00125-012-2597-y/fulltext.html In the mid-1990s, researchers began to re-examine type 2 diabetes from a more 'lipocentric' perspective; giving strong consideration to the idea that systemic lipid imbalances give rise to glucose dysregulation, rather than vice versa. At the forefront of this paradigm shift was a report by Krssak and colleagues (Diabetologia 1999; 42:113-116) showing that intramyocellular lipid content, measured via the (then) novel application of proton nuclear magnetic resonance spectroscopy, served as a robust indicator of muscle insulin sensitivity in healthy individuals. A subsequent wave of investigations produced compelling correlative evidence linking ectopic lipid deposition within skeletal myocytes to the development of obesity-associated insulin resistance. But this relationship has proven much more complex than originally imagined, and scientists today are still left wondering if and how the intramyocellular accumulation of lipid droplets has a direct bearing on insulin action. Originally viewed as a simple storage depot, the lipid droplet is now recognised as an essential and sophisticated organelle that actively participates in numerous cellular processes. This edition of 'Then and now' revisits the connection between intramuscular lipids and insulin resistance and looks to future research aimed at understanding the dynamic interplay between lipid droplet biology and metabolic health. DOI: 10.1007/s00125-012-2597-y PMID: 22660796 ------------ [3] J Clin Endocrinol Metab. 2001 Dec;86(12):5755-61. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. Goodpaster BH(1), He J, Watkins S, Kelley DE. Author information: (1)Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. bgood+@pitt.edu We examined the hypothesis that an excess accumulation of intramuscular lipid (IMCL) is associated with insulin resistance and that this may be mediated by the oxidative capacity of muscle. Nine sedentary lean (L) and 11 obese (O) subjects, 8 obese subjects with type 2 diabetes mellitus (D), and 9 lean, exercise-trained (T) subjects volunteered for this study. Insulin sensitivity (M) determined during a hyperinsulinemic (40 mU x m(-2)min(-1)) euglycemic clamp was greater (P < 0.01) in L and T, compared with O and D (9.45 +/- 0.59 and 10.26 +/- 0.78 vs. 5.51 +/- 0.61 and 1.15 +/- 0.83 mg x min(-1)kg fat free mass(-1), respectively). IMCL in percutaneous vastus lateralis biopsy specimens by quantitative image analysis of Oil Red O staining was approximately 2-fold higher in D than in L (3.04 +/- 0.39 vs. 1.40 +/- 0.28% area as lipid; P < 0.01). IMCL was also higher in T (2.36 +/- 0.37), compared with L (P < 0.01). The oxidative capacity of muscle determined with succinate dehydrogenase staining of muscle fibers was higher in T, compared with L, O, and D (50.0 +/- 4.4, 36.1 +/- 4.4, 29.7 +/- 3.8, and 33.4 +/- 4.7 optical density units, respectively; P < 0.01). IMCL was negatively associated with M (r = -0.57, P < 0.05) when endurance-trained subjects were excluded from the analysis, and this association was independent of body mass index. However, the relationship between IMCL and M was not significant when trained individuals were included. There was a positive association between the oxidative capacity and M among nondiabetics (r = 0.37, P < 0.05). In summary, skeletal muscle of trained endurance athletes is markedly insulin sensitive and has a high oxidative capacity, despite having an elevated lipid content. In conclusion, the capacity for lipid oxidation may be an important mediator of the association between excess muscle lipid accumulation and insulin resistance. DOI: 10.1210/jcem.86.12.8075 PMID: 11739435 [4] Irwin ML, Yasui Y, Ulrich CM, et al. Effect of exercise on total and intra-abdominal body fat in postmenopausal women: a randomized controlled trial. Journal of the American Medical Association. 2003;289(3):323–330. [PubMed] [5] Cuff DJ, Meneilly GS, Martin A, Ignaszewski A, Tildesley HD, Frohlich JJ. Effective exercise modality to reduce insulin resistance in women with type 2 diabetes. Diabetes Care. 2003;26(11):2977–2982. [PubMed] [6] Gan SK, Kriketos AD, Ellis BA, Thompson CH, Kraegen EW, Chisholm DJ. Changes in aerobic capacity and visceral fat but not myocyte lipid levels predict increased insulin action after exercise in overweight and obese men. Diabetes Care. 2003;26(6):1706–1713.[PubMed] 6. Duncan GE, Perri MG, Theriaque DW, Hutson AD, Eckel RH, Stacpoole PW. Exercise training, without weight loss, increases insulin sensitivity and postheparin plasma lipase activity in previously sedentary adults. Diabetes Care. 2003;26(3):557–562. [PubMed] Quote Link to comment Share on other sites More sharing options...
mikeccolella Posted July 26, 2016 Report Share Posted July 26, 2016 (edited) So Dean how would you sum it up for us dummies. My take is lots of intense exercise/running etc., resistance training several days a week, cold exposure 2 or more hours a day and say 40% fat. And yes I know Here I go again contradicting myself because I recently posted I was not going to micromanage, but your posts are irresistibly fascinating!!! Also I thought you had decided intense/endurance exercise was not a good thing in anything like what these mice were doing? "Do I contradict myself? Very well, then I contradict myself, I am large, I contain multitudes" Walt Whitman Edited July 26, 2016 by mikeccolella Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 26, 2016 Author Report Share Posted July 26, 2016 Mike, So Dean how would you sum it up for us dummies. My take is lots of intense exercise/running etc., resistance training several days a week, cold exposure 2 or more hours a day and say 40% fat. That sounds about right. If I were to include several bonus tips, they'd be: Don't skimp on the calories, but maintain a net calorie shortfall to stay slim Add whole body vibration therapy for 10min a few times per week Practice the meditation/yoga variant of your choice Avoid contracting CMV through the indiscriminate exchange of bodily fluids. :-) P.S. my family and I are traveling to Niagara Falls for the next few days, so my replies may be delayed, and new posts postponed until I return. I expect there are some folks who'll appreciate a break from my deluge. --Dean Quote Link to comment Share on other sites More sharing options...
mikeccolella Posted July 26, 2016 Report Share Posted July 26, 2016 I won't but you deserve a break. Have a great trip! Quote Link to comment Share on other sites More sharing options...
Gordo Posted July 26, 2016 Report Share Posted July 26, 2016 Gordo, still think the combination of cold exposure and endurance exercise is a counterproductive waste of time and energy? Yes, I do :) I still love that we have quite different approaches and hope it stays that way, it will be interesting to see as more (if more?) people get involved, which approach the data ends up favoring (or perhaps there is no favorite). We both get 30-40% of calories from mostly unsaturated, plant based fat, so at least we agree on that, we also agree on the fact that muscles are a great tool for glucose control and are integral to optimal CE results. I'm all about finding the most efficient ways of doing things. I never said no good could come from endurance exercise, but so far nothing that you have posted has convinced me that routine endurance exercise is the most efficient (optimal) way of reaching any of our health and longevity goals. One must also consider the downsides of serious regular endurance exercise - wearing out your joints and depleting your body of important resources. As you've pointed out, muscle mass is important for health and longevity (maximizing the benefits of CE), this is something I've been pounding the table on for a while. Is it more efficient to build muscle mass via 9 hours of stationary biking, 2 hours of jogging, or 10 minutes of intense anaerobic exercise like sprints, weight vest stair runs, pull ups, and hanging crunches? Excessive endurance exercise can in fact actually lead to net muscle loss. Comparing photos of different types of athletes should tell you which style results in muscle gains -- that said there aren't a whole lot of muscle bound athletes that eat a low protein plant based whole food diet and just being muscular in and of itself is NOT the goal and in fact many of the things people do to become muscular are counterproductive to health and longevity (particularly when it comes to diet and supplements). Quote Link to comment Share on other sites More sharing options...
drewab Posted July 26, 2016 Report Share Posted July 26, 2016 P.S. my family and I are traveling to Niagara Falls for the next few days, so my replies may be delayed, and new posts postponed until I return. I expect there are some folks who'll appreciate a break from my deluge. --Dean Dean is gone. That means we can have a party and eat his favourite food. Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted July 26, 2016 Report Share Posted July 26, 2016 He'll come back to an empty pantry and a devastated "CR garden". But he must give us a full report on what he ate on vacation - cause that's always a problem for me... mostly, I just go off diet altogether when vacationing abroad - I start of trying to keep it together, but by the end of the first week, I usually delve into the local cuisine, especially if I'm somewhere exotic or simply renowned for great food (South of France, anybody...) :) Quote Link to comment Share on other sites More sharing options...
Gordo Posted July 28, 2016 Report Share Posted July 28, 2016 (edited) On my recent 2 week road trip I tried to keep the diet, but ended up having "special exceptions". I did bring a cooler full of my usual foods though. We stopped at several supermarkets and loaded up on produce during the trip. There are actually a LOT of chain type places to buy good plant based whole food meals. Panera has a pretty nice cobb avocado salad that you can customize out the wazoo substituting the meat parts that normally come with it for all sorts of plant based goodness (best to do this using their app and just put your order in via the app). Chipotle, despite all the recent critics, is a great stop too -- I get their "bowl" full of black AND pinto beans (just ask for both and they will do it), brown rice, guac, tomatoes, peppers, onions, corn, lettuce. The Cheesecake Factory has a phenomenal "Super Antioxidant Salad" (yes, they actually call it that). Anyway, so as not to stray off topic too much... First - the cheap cooling towels arrived yesterday from China (I was surprised they arrived so quickly). They are GREAT, I highly recommend these things, I had one draped over me last night while under a ceiling fan and the evaporative cooling was quite strong. I need to look for a shirt made out of the same material. In other news, we had recently discussed the most efficient ways of building muscle mass (for longevity promoting health benefits in particular with respect to cold exposure). My approach is HITT style bodyweight exercises, the following video is an example of this, and the guy in the video, Frank Medrano, is a vegan by the way: https://youtu.be/RFPsvF3UOdo Here is an example of the type of body transformation that can be achieved with this style of workout, it starts with a 100 lb. wimp: https://youtu.be/nqbFPN0SkLI But this vegan bodybuilder's philosophy is probably closest to my own except that I believe in a lower BMI/lower calories: https://youtu.be/amJ_oatZ0zY These guys inspired me to install a pull up bar in my bedroom, it was a fun project, it hangs down from the ceiling and is mounted up in the attic, I just used simple, inexpensive galvanized pipe and pipe connectors from Home Depot. Since its right next to the bed, I have no excuses not to use it, and I do use it, pretty much every single day. My family also started using it: Even my 4 year old daughter can do pull ups with a little assist (found that stretch band thing on Amazon): (she even has great form) -Gordo Edited August 5, 2016 by Gordo Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 30, 2016 Author Report Share Posted July 30, 2016 Last week in this post I pointed to these ice packs on Amazon as alternatives to the ones sold with the Cool Fat Burner for 1/10th the price. They arrived and I had a chance to test them out today. They are indeed slightly longer and slightly heavier than the CFB ice packs. But they fit nicely in the pockets of both models of the CFB, and they seem to hold their temperature for approximately as long as the solid packs from CFB. So I highly recommend them for people looking for less expensive alternatives to the ice packs offered by CFB. On a related note. I've discontinued my recent practice of wearing the CFB without a shirt, since I just noticed a bit of numbness to the touch in my shoulders, which has persisted for at several hours after removing the CFB. Don't want to overdo it... ☺ --Dean Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 30, 2016 Author Report Share Posted July 30, 2016 Fiber Boosts BAT and WAT Browning Too! Here is yet another BAT Rule1 example - this time it's dietary fiber. This new study [1] found that both oat and wheat fiber boost BAT and the browning of WAT, and helps to prevent obesity induced by a high fat diet. In the study, researchers used seven-week-old male C57BL/6J mice housed at normal lab temperatures (22 °C). For 24 weeks they fed them either normal chow (Chow), a high fat diet (HFD), HFD + Oat fiber (H-oat) or HFD + Wheat fiber (H-wheat). The fibers accounted for 0.8% of diet by weight, and was mixed into their food. The two HFD fiber groups gained less weight than the HFD-only group, and slightly more than the Chow-fed group. Protein Kinase A (PKA) which you'll recall is central to the "alternative anabolic pathway" I outlined most recently here, was higher in BAT in the H-wheat group and especially higher in WAT in the H-oat group as illustrated by the yellow bars below: Other signs of browning were that Oat fiber increased expression of UCP1 in WAT, and both fibers boosted longevity-promoting FGF-21 as well as mitochondria-biosynthesis-promoting PGC-1α in both BAT and WAT. The activity of the β3 adrenergic receptor, which detects elevated norepinephrine that results from, among other things, cold exposure, was also increased by the fiber diets. The authors conclude: The present study suggests that cereal dietary fiber reduced high-fat-induced obesity by enhancing adipocyte lipolysis and consequently reduce visceral fat mass in response to HFD feeding. ... We found cereal dietary fiber both strengthened fat mobilization by cAMP-PKA-HSL pathway in WAT, and promoted WAT browning by activation UCP1 and β3AR, PGC-1α, FGF-21, involved in thermogenesis, thereby reducing obesity. It's funny. I just recently ran out of the oat fiber samples I'd gotten for free of from Creafill, and instead ordered this oat fiber from Amazon. Ironically, I just received it today, the same day I discovered this study showing oat fiber helps brown WAT and boost BAT. The oat fiber from Amazon It is a really nice fine powder, which I'll be using as part of my fiber mix (which also includes psyllium, potato starch & plantain flour) to thicken my blended fruit & veggie "salad dressing" - which Saul foolishly criticizes. I've added dietary fiber to the master list of BAT inducers and WAT browning agents below. --Dean ---- 1BAT Rule - Virtually every dietary or lifestyle intervention that is known to be healthy is also associated with an increase in BAT activity, browning of white fat and/or thermogenesis. ---------------- Here is the latest full list of modifiable and [nonmodifiable] factors associated with increased brown/beige adipose tissue and/or thermogenesis, with the factors mentioned in this post highlighted in red: Cold exposure - by far the best BAT inducer/activator Spicy / pungent foods, herbs & supplements - capsaicin / chilli peppers, curcumin / turmeric root, menthol/mint/camphor, oregano, cloves, mustard, horseradish/wasabi, garlic, onions Sulforaphane-rich foods - Broccoli, brussels sprouts, cabbage Nitrate-rich foods - beets, celery, arugula, and spinach Arginine-rich foods - Good vegan sources include seeds (esp. sesame, sunflower & pumpkin), nuts (esp. almonds and walnuts) and legumes (esp. soy, lupin & fava beans and peas) Citrulline-rich foods - Highest by far in watermelon, but also some in onions, garlic, onions, cucumber, other melons & gourds, walnuts, peanuts, almonds, cocoa, chickpeas Luteolin-rich foods - Herbs (thyme, parsley, oregano, peppermint, rosemary), hot peppers, citrus fruit, celery, beets, spinach, cruciferous veggies, olive oil, carrots. Healthy Fats - DHA / EPA / fish-oil, MUFA-rich diet, Extra Virgin Olive Oil Fiber - Especially cereal fiber (wheat and oat fiber) Olive Polyphenols - Extra Virgin Olive Oil / Olive Leaf Extract / Olive Leaf Tea Other foods - Apples / apple peels / ursolic acid; Citrus fruit / citrus peels / limonene; Honey / chrysin Beverages - green tea, roasted coffee, red wine, cacao beans / chocolate Low gluten diet Methionine restriction - Reduce animal protein. Soy is low in methionine and high in arginine, but also high in leucine. Leucine restriction - Reduce animals protein. Leucine is highest in beef, fish, eggs, cheese and soy. Low protein diet Drugs / Supplements - metformin, berberine, caffeine, creatine, nicotinamide riboside (NAD), resveratrol, ginseng, cannabidiol / hemp oil / medicinal marijuana, melatonin Time Restricted Feeding - most calories at breakfast Exercise & elevated lactate / lactic acid Acupuncture - locations Zusanli (foot - ST36) and Neiting (lower leg - ST44) Whole body vibration therapy Avoid obesity/overweight [being naturally thin - high metabolic rate] [being younger] [being female] [Ethnicity - having cold-climate ancestors] [being of genotype TT for rs1800592 and AA for rs4994 as reported by 23andMe] ------------ [1] Nutrition. 2016 Jun 2. pii: S0899-9007(16)30079-X. doi: 10.1016/j.nut.2016.05.006. [Epub ahead of print] Lipolysis and thermogenesis in adipose tissues as new potential mechanisms for metabolic benefits of dietary fiber. Han SF1, Jiao J2, Zhang W2, Xu JY3, Zhang W4, Fu CL2, Qin LQ5. Full text: http://sci-hub.cc/10.1016/j.nut.2016.05.006 Abstract OBJECTIVE: Dietary fiber consumption is associated with reduced risk for the development of noncommunicable diseases. The aim of the present study was to evaluate the effects of cereal dietary fiber on the levels of proteins involved in lipolysis and thermogenesis in white adipose tissue (WAT) and brown adipose tissue (BAT) of C57 BL/6 J mice fed a high-fat diet (HFD). METHODS: Male C57BL/6 J mice were fed normal chow diet (Chow), HFD, HFD plus oat fiber (H-oat), or HFD plus wheat bran fiber (H-wheat) for 24 wk. Body weight and food intake were recorded weekly. Serum adiponectin was assayed by an enzyme-linked immunosorbent assay kit. Western blotting was used to assess the protein expressions of adipose triacylglycerol lipase (ATGL), cAMP protein kinase catalytic subunit (cAMP), protein kinase A (PKA), perilipin A, hormone-sensitive lipase (HSL), uncoupling protein 1 (UCP1), fibroblast growth factor 21 (FGF-21), β3-adrenergic receptor (β3AR), and proliferator-activated receptor gamma coactivator-1 α (PGC-1 α) in the WAT and BAT. RESULTS: At the end of the feeding period, body and adipose tissues weight in both H-oat and H-wheat groups were lower than in the HFD group. Mice in the H-oat and H-wheat groups showed an increasing trend in serum adiponectin level. Compared with the HFD group, cereal dietary fiber increased protein expressions involved in the lipolysis and browning process. Compared with the H-wheat group, H-oat was more effective in protein expressions of PKA, PGC-1 α, and UCP1 of the WAT samples. Compared with the H-oat group, H-wheat was more effective in protein expressions of PKA, ATGL, UCP1, β3AR, and FGF-21 of the BAT samples. CONCLUSIONS: Taken together, our results suggested that cereal dietary fiber enhanced adipocyte lipolysis by the cAMP-PKA-HSL pathway and promoted WAT browning by activation of UCP1, and consequently reduced visceral fat mass in response to HFD feeding. Copyright © 2016 Elsevier Inc. All rights reserved. PMID: 27461561 Quote Link to comment Share on other sites More sharing options...
Recommended Posts
Join the conversation
You can post now and register later. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.