607 replies to this topic

[Gordo]

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.

[Gordo]

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 by Gordo, 20 July 2016 - 05:47 PM.

[Dean Pomerleau]

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....les/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

[Dean Pomerleau]

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:

 

 

 

 

[Gordo]

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.

[mikeccolella]

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

[Dean Pomerleau]

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.metabolis...0002-6/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

[Dean Pomerleau]

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

 

[TomBAvoider]

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.

[Dean Pomerleau]

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

[Dean Pomerleau]

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....les/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

[mikeccolella]

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.

[Dean Pomerleau]

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...tm?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

[TomBAvoider]

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

Introduction

During 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.

Methods

Thirty-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).

Results

Participants 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.

Conclusions

We 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.

[Dean Pomerleau]

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

[Dean Pomerleau]

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 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.

 

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.front...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...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]

[mikeccolella]

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 by mikeccolella, 26 July 2016 - 08:05 AM.

[Dean Pomerleau]

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

[mikeccolella]

I won't but you deserve a break. Have a great trip!

[Gordo]

 

 

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).