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Dean Pomerleau

Cold Exposure & Other Mild Stressors for Increased Health & Longevity

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Thanks to Al Pater for sending me a pointer to this study [1] characterizing BAT in humans. From the full text, it appears that cold exposure can greatly increase the amount of BAT a person has, and it has a significant effect on one's metabolic rate:

 

In healthy lean male and female adults (mean 6 SD age 40 6 9 years), mean weight of cold-activated human BAT calculated by PET-CT was 34 g (range 9–90) (8). ... That estimate compares with the mean 151 g (range 29–296) in cold-exposed young men (9)... Based on the calculation of 63 g cervical BAT reported in a different study by Virtanen et al. (7), it was estimated that activated BAT thermogenesis contributed 4.5% to whole body energy expenditure, which was considered to be significant (23) and commensurate with the goal of exploiting BAT to burn excess calories stored in WAT for weight loss in obesity and type 2 diabetes (3). The 5% figure cited above could be an underestimate by a factor of two to three in some subjects because of their greater BAT mass.

 

What's pretty amazing to me is that so little active brown adipose tissue (e.g. 150g or 1/3 of a pound) can contribute as much as 10-12% of whole body energy expenditure. Those are some active fat cells!

 

The paper goes on to discuss in excruciating detail the distribution of BAT around the body and its evolutionary purpose (to generate heat in order to keep key organs warm). Regarding distribution of BAT, the bottom line appears to be that most of it is located in the upper chest, upper back, and along the spine. Here is a pretty cool image of someone with a lot of activated BAT:

 

What-is-BAT-.jpg

 

It talks about how obese and diabetic people have less BAT, and less BAT activity, than lean people (yeah for us!):

 

Obesity is associated with a reduction in BAT activity
(6,44) but the extent to which obesity is cause or effect or
involved in a vicious cycle or energy intake exceeding
expenditure remains to be established.

 

It discusses various ways of increasing/activating BAT in obese/diabetic people, including cold exposure "if tolerated by people". The authors speculate about the alternative possibility of injecting harvested and cultured BAT cells either into the neck region or abdominal region of obese people to trigger thermogenesis and energy expenditure. Seems pretty extreme, when cold exposure seems to be able to accomplish BAT activation, without the surgery.

 

--Dean

 

------------

[1] Diabetes. 2013 Jun;62(6):1783-90. doi: 10.2337/db12-1430.

Anatomical locations of human brown adipose tissue: functional relevance and
implications in obesity and type 2 diabetes.

Sacks H(1), Symonds ME.

Author information:
(1)Endocrinology and Diabetes Division, VA Greater Los Angeles Healthcare System,
Los Angeles, California, USA. hsacks@hotmail.com

 

Free full text: http://diabetes.diabetesjournals.org/content/62/6/1783.full.pdf+html

We will review information about and present hypotheses as to the anatomy of
brown adipose tissue (BAT). Why is it located where it is in humans? Its
anatomical distribution is likely to confer survival value by protecting critical
organs from hypothermia by adaptive thermogenesis. Ultimately, the location and
function will be important when considering therapeutic strategies for preventing
and treating obesity and type 2 diabetes, in which case successful interventions
will need to have a significant effect on BAT function in subjects living in a
thermoneutral environment. In view of the diverse locations and potential
differences in responsiveness between BAT depots, it is likely that BAT will be
shown to have much more subtle and thus previously overlooked functions and
regulatory control mechanisms.

PMCID: PMC3661606
PMID: 23704519

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All,

 

Before anyone (else) considering experimenting with cold exposure goes out and buys the TechKewl cooling vest I pointed to earlier, which sounds like it may not be a great fit for small folks like many of us, you might want to consider this other product I discovered, the Cool Fat Burner (CFB). It comes in two styles and a variety of sizes. The "original" style costs $86 including tax and shipping.

 

It comes in two styles:

 

                     Original ($86 incl S&H)     "Gut Buster" Vest ($106 incl S&H)            

 

cfb.jpgcgb-208x240.jpg

 

 

 

Here is what the "original" looks like on someone:

 

lxyrxyug5ygxkarct4it.jpg

 

Given that most BAT is located in the clavicle region and is responsive to local cooling, this original form factor makes sense. If you're only going to buy one of them, it seems to me therefore the original version is the way to go. But if you buy both together you get a 25% discount...

 

They've got some pretty cool scientific tests and case studies of brown fat activation as a result of using the CFB. Consistent use definitely appears to promote the generation and activation of BAT. 

 

I haven't bought any vest yet - it's still a "balmly" 14F outside in Pittsburgh, and 58F in my basement "man cave" so extra cooling isn't yet required. But I'll probably give this one a try.  It comes with a 60-day, 110% guarantee if not completely satisfied.

 

--Dean

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All,

 

In my continuing quest to find ways to maximize brown adipose tissue (BAT) activity, this study [1] found that a low protein diet was conducive to high BAT activity, independent of whether the protein was replaced by carbohydrates or fats. This is interesting because protein restriction is yet another intervention that is thought to be healthy and potentially extend lifespan, in fact some people think protein restriction may be the way calorie restriction actually has its benefits. 

 

So protein restriction can be added to the growing list of interventions that activate BAT and also are thought to be health / lifespan promoting. The list now includes:

  • Cold exposure - by far the best BAT activator
  • Metformin
  • Green Tea
  • Caffeine
  • Capsaicin
  • A low protein diet

The fact that so many compounds and interventions thought to be healthy are BAT activators suggests to me that BAT may be an important contributor to health and longevity.

 

 

--Dean

 

---------------

[1] J Nutr. 1987 Oct;117(10):1721-6.

Influence of carbohydrate and fat intake on diet-induced thermogenesis and brown
fat activity in rats fed low protein diets.

Rothwell NJ(1), Stock MJ.

Author information:
(1)Department of Physiology, St. George's Hospital Medical School, Tooting,
London, United Kingdom.

Voluntary intake of protein, fat and carbohydrate (CHO) was modified by feeding
young rats either a control purified diet [% metabolizable energy (ME): protein
21, fat 7, CHO 72], a control diet plus sucrose solution (20%) to drink (final
intakes 17, 6 and 77% ME as protein, fat and CHO, respectively) or a low protein
diet substituted with either CHO (8, 7 and 85% ME as protein, fat and CHO,
respectively) or fat (8, 20 and 72% ME as protein, fat and CHO, respectively).
Total ME intakes corrected for body size were similar for all rats, but body
weight, energy gain and net energetic efficiency were lower in both low
protein-fed groups than in the control group. The acute thermogenic response (%
rise in oxygen consumption) to a standard balanced-nutrient meal was higher (12%)
in sucrose-supplemented and in low protein groups (15-16%) than in control rats
(8%). Brown adipose tissue protein content and thermogenic capacity (assessed
from purine nucleotide binding to isolated mitochondria) were greater than
control values in sucrose-fed and protein-deficient animals, and the greatest
levels of activity were seen in low protein-fed rats with a high fat intake. The
results demonstrate that the changes in energy balance, thermogenesis and brown
adipose tissue activity that result from protein deficiency cannot be ascribed to
changes in the level of energy intake or to a specific increase in the amount or
proportion of either CHO or fat. They suggest that the protein-to-energy ratio
must be the primary influence on thermogenesis and brown fat activity in these
animals.

PMID: 3668686 

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Here is an interesting new study [1] (press release) thanks to Al Pater. It found that mice exposed to cold lost weight, at least for the first few weeks, as a result of increased BAT-mediated thermogenesis - no surprise.

 

But what was surprising was the mechanism they discovered by which cold exposure appeared to influence BAT - namely via the mice's gut bacteria. At the bottom is the helpful graphical abstract from the full text helps to illustrate what the researchers did, and what they found. FIrst they exposed two groups of mice to either cold or normal (warm) conditions for 10 days. The gut microbiome of the cold-exposed mice (the "cold microbiome") was dramatically different from the microbiome of the warm mice (the "warm microbiome"). They then transferred the cold and warm microbiomes to two different groups of germ-free mice. Surprisingly, receiving the cold microbiome resulted in the conversion of white adipose tissue (WAT) to brown (or beige) adipose tissue (BAT), with an accompanying increase in insulin sensitivity and thermogenesis - all without ever being exposed to cold!

 

The mice that received the cold microbiome initially lost weight as a result of increased thermogenesis. But remarkably, after several weeks the weight loss stopped despite no change in food intake. What they discovered was that the cold microbiome caused the mice's intestine to grow in size and triggered an increase in the surface area of intestinal cells that absorb nutrients. The lead researcher said:

 

"These findings demonstrate that gut microbes enable mammals to harvest more energy from food as a way to adapt to the increased energy demand associated with long periods of cold exposure, thereby helping to protect against hypothermia," Trajkovski says. "We were surprised to see that gut microbes had such dramatic effects on the structure and function of the intestine."

 

This is yet another dramatic illustration of how important and influential the gut microbiome is for health. It suggests, at least theoretically, one more intervention for increasing BAT expression - get a poop transplant from someone who have undergone consistent exposure to cold :-).

 

--Dean

 

oaw05s0.png

 

 

-------------

[1] Cell. 2015 Dec 3;163(6):1360-74. doi: 10.1016/j.cell.2015.11.004.

 

Gut Microbiota Orchestrates Energy Homeostasis during Cold.

 

Chevalier C, Stojanovic O, Colin DJ, Suarez-Zamorano N, Tarallo V, Veyrat-Durebex C, Rigo D, Fabbiano S, Stevanovic A, Hagemann S, Montet X, Seimbille Y, Zamboni N, Hapfelmeier S, Trajkovski M.

 

Full text: http://linkinghub.elsevier.com.sci-hub.io/retrieve/pii/S0092-8674(15)01484-1

Highlights

Cold exposure leads to marked changes in the gut microbiota composition

Cold microbiota transplantation increases insulin sensitivity and WAT browning

Cold exposure or cold transplantation increase the gut size and absorptive capacity

Reconstitution of cold-suppressed A. muciniphila reverts the increased caloric uptake

Abstract

Microbial functions in the host physiology are a result of the microbiota-host co-evolution. We show that cold exposure leads to marked shift of the microbiota composition, referred to as cold microbiota. Transplantation of the cold microbiota to germ-free mice is sufficient to increase insulin sensitivity of the host and enable tolerance to cold partly by promoting the white fat browning, leading to increased energy expenditure and fat loss. During prolonged cold, however, the body weight loss is attenuated, caused by adaptive mechanisms maximizing caloric uptake and increasing intestinal, villi, and microvilli lengths. This increased absorptive surface is transferable with the cold microbiota, leading to altered intestinal gene expression promoting tissue remodeling and suppression of apoptosis-the effect diminished by co-transplanting the most cold-downregulated strain Akkermansia muciniphila during the cold microbiota transfer. Our results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand.

 

PMID: 26638070

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It is interesting to note that women generally have more BAT than men, and they generally live longer, I do wonder if there is a connection there.

 

Is there evidence that cooling specific body parts such as the clavicle area where BAT is more common actually results in increased BAT formation vs. other types of cooling?  Some of the studies Dean posted links to showed increases in BAT when subjects were only getting direct cooling to their legs (where little to no BAT exists).

 

Regarding the Techkewl vest, I've done a bit more experimentation with it.  With a complete charge (still not sure how long that takes, I had mine in a deep freezer for many days) the vest will cool for up to 5 hours.  The vest has 4 cooling panels, each consisting of 4 sealed packs (16 packs in all).  After 4 hours, 2 out of the 16 PCM packs were 100% liquid, but overall I would estimate about 80% phase change had occurred. After 5 hours the vest was still cooling, and 7 out of 16 packs were 100% liquid but 95% phase change had occurred overall.  I had done a light HIIT exercise routine during this period, stair runs and pull ups, while wearing the vest, house temps were between 70-75 the whole time.

 

Also I found that just putting a belt around the vest between its velcro straps results in an excellent fit with all 16 PCM packs making solid contact to my body.  

techkewl.jpg

 

Note that simply by pulling the two front cooling panels upward, although probably not designed for this, the vest works very well for directly cooling both the neck and clavicle areas where BAT is most prevalent and seems to stay in place surprisingly well even when walking around.  The total PCM material looks to be possibly double (or more?) in the techkewl vs. the cool fat burner (although that is hard to tell just from pictures).  If you were only interested in cooling the neck/clavicle area, you could just use two of the four techkewl PCM panels and always have one set in the freezer for continuous cooling by swapping out the panels every 4-5 hours.

 

Example with front panels pulled up, covering the clavicles:

 

techkewlclav.jpg

I doubt it would be necessary but you could also put something into the bottom of the vest PCM panel pockets like a sponge or a sock that would make it impossible for the panel to move back down from the raised position shown.

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Gordo,


Thanks for all the helpful information about the TechKewl vest. It sounds much better than the impression I got from your initial review. The belt looks like a very good idea, and your observation that a charge lasts 4-5 hours sounds great!


 


Yes, I'd watched that Cool Fat Burner video and found it pretty helpful. For a product you'd expect to be a total weight loss scam, the inventor (I presume) does some pretty interesting and well-documented self-experiments. He's a man after my own heart! He does have quite a bit of BAT all over his torso, as the PET scan in the video shows. But even for him (with a lot of cold exposure under his belt) it appears concentrated towards the upper chest and shoulders. This Huffington Post article (comparing BAT in caucasians vs. asians - caucasians have more, and lower diabetes risk, suggesting a link there) has a better picture of six men (3 caucasian and 3 asian) with their distribution of BAT:


 


o-SOUTH-ASIAN-BROWN-FAT-570.jpg?2


 


It looks to me like while some of the men have pockets of BAT all around the chest cavity, the largest, most consistent and most active concentration of BAT is in the shoulders, clavicle area and around the trapezius muscle in the upper middle of the back. Here is where BAT is located as described in this NY Times article:


 


There was not much brown fat, just a few ounces in the upper back, on the side of the neck, in the dip between the collarbone and the shoulder, and along the spine.


 


While I'm not certain focusing the cooling on those spots will be more effective than cooling elsewhere on the body - it seems reasonable to suppose based on the fact that BAT activation is temperature dependent and that placing the cooling source near it will likely affect its temperature more than cooling more distant parts of the body, particularly in spots where the BAT deposits are near the surface, like at the neck, shoulders and trapezius area.


 


I can't really tell where on the TechKewl vest the cooling packs themselves are located based on your pictures. Do they extend up to and above the horizontal seam in the photo just above the logo on the chest? Similarly, how high do the packs go in the back? If the packs don't extend that high it would seem that they aren't really hitting the shoulder/clavicle/trapezius area very well, even when hiked up.


 


Regarding women having more BAT than men - I wasn't aware of that. But it appears you are correct! Here is an article from back in 2009 when it was discovery that adult humans have significant brown fat, contrary to previous thinking. Here is a quote from the article:


 


They also discovered that brown fat is most abundant in young women and least frequent in older, overweight men. In fact, women were more than twice as likely as men to have substantial amounts of brown fat.


 


"One theory for this is that women may have less muscle mass overall, so they need more brown fat to generate heat and keep warm," Cypess said.


 


 Stay tuned for my next post in this thread where I'll discuss the topic of women, leanness and BAT prevalence...

 

--Dean

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All,

 

As promised in my previous post, more on the topic of leanness and brown adipose tissue (BAT) prevalence...

 

I came across this 2013 study [1] which is quite interesting, and potentially important for lean CR folks hoping to generate and activate BAT.

 

They tested BAT activity via a PET scan at relatively mild ambient temperatures (low 70s F) in 38 women divided into four different groups:

  1. Constitutionally Lean (CL) women (avg. BMI 16.2) - "Constitutional leanness is a peculiar physiological condition whereby the body is resistant to fat storage, even in overfeeding conditions." That is, women who were naturally skinny without CR.
  2. Anorexic women (AN) women (avg BMI 15.5)
  3. Recovered anorexic (R-AN) women (avg BMI 18.8)
  4. Normal weight control (NW) women (avg BMI 22.2)
Note they were all a pretty thin bunch of women by American standards, even the normal weight controls.

 

Here is the most important thing they found:

 


 All CL (100%), none of the AN and refed AN (0%), and 3 of the 24 NW (12%) subjects showed [measureable BAT activity].


 

So it was really only the naturally thin women who had active BAT, neither the anorexics nor the normal weight women had much if any. Furthermore, even in the 3 (of 24) normal weight women who appeared to have some BAT, they had only half as much BAT activity as the constitutionally lean women.

 

Interestingly, they found:


 

In [the constitutionally lean women], the [measure of BAT activity] was ... inversely correlated

with respiratory quotient.

 

From the full text of [1], here is the graph illustrating this relationship, with respiratory quotient (RQ) along the X-axis and a measure of BAT activity on the Y-axis. As you can see, a pretty strong inverse linear relationship (r = 0.74).

 

zMUe8yS.png

 

For those who don't know, respiratory quotient (RQ) is basically a measure of how much fat vs. carbohydrates an organism is burning. A high RQ (towards the right side of the graph) means you are burning a lot of carbs. A low RQ (towards the left side of the graph) means you are burning a lot of fat. Protein is in the middle. What this statement and the corresponding graph are saying/showing is that the naturally thin women with the most BAT activity were the ones who were burning the most fat relative to carbohydrates.

 

This makes sense, since BAT preferentially burns fat rather than carbohydrates. But it suggests that for those of us without much (white) adipose tissue (i.e. with a low percentage body fat) for the BAT to burn, it will be best to consume sufficient fat in our diet to enable BAT to form and be active. I guess it's good (for BAT activity anyway) that I'm eating quite a bit of fat mostly from nuts, seeds and avocados (in fact both Michael and Sirtuin say I'm eating a "stupid high" amount of such fat :-) ) - rather than a high carb diet I was previously following.


 

Finally, they found:

 


In [the constitutionally lean women], the [measure of BAT activity] was directly correlated to resting metabolic rate...

 


Here is the graph backing up this finding, with metabolic rate along the X-axis and a measure of BAT activity along the Y-axis. It is a pretty clear and dramatic linear relationship (r = 0.81) - a higher metabolic rate equates with more BAT activity:

 

TT8I6an.png

 

 

This suggests that these women were naturally thin because of their higher resting metabolic rate, which resulted from their elevated level of BAT activity.

 

This is interesting in light of the fact that many of us "naturally thin" CR practitioners have been bemoaning (e.g. in this extended thread) the fact that we may not benefit from CR as much as naturally "thrifty" people who tend retain a lot of weight because we can't cut calories as much as they can without losing too much weight.

 

The results of this study can be interpreted to suggest quite the opposite. Namely, it seem to suggest that being "naturally thin" may be a result of having more (active) brown fat. And if the hypothesis that I've been promulgating throughout this thread is correct, namely that burning calories "cleanly" via BAT-mediated thermogenesis may be beneficial and perhaps even critical for CR lifespan benefits, than we naturally thin folks may actually have an advantage over our chubbier counterparts, because we have more (active) brown fat.

 

But the other thing to think about for everyone practicing CR is the results seen in the anorexics in this study. They are obviously quite thin (BMI 15.5!), almost certainly had a relatively low core body temperature and obviously a low percentage of regular (white) adipose tissue, just like most serious CR practitioners. But none of them, not even the one's who had recovered and had a BMI of nearly 19, had any measureable BAT activity. 

 

This suggests that unless one is naturally quite thin and has a high metabolic rate, simply practicing CR and hoping you'll develop BAT simply because you feel cold much of the time, isn't likely to cut it.

 

In other words, you won't have much BAT unless you actively expose yourself to cold. And further, you need to literally be cold rather than simply feel cold in otherwise warm conditions, to generate BAT.

 

--Dean

 

------------------------

[1] J Clin Endocrinol Metab. 2013 Mar;98(3):1214-8. doi: 10.1210/jc.2012-2981. Epub

 

2013 Feb 7.

 

Evidence of brown fat activity in constitutional leanness.

 

Pasanisi F(1), Pace L, Fonti R, Marra M, Sgambati D, De Caprio C, De Filippo E,

Vaccaro A, Salvatore M, Contaldo F.

 

Author information:

(1)Federico II University of Naples, Department of Clinical Medicine and Surgery,

Via Pansini 5, Naples, Italy. pasanisi@unina.it

 


 

BACKGROUND: Brown adipose tissue (BAT) was considered essentially nonexistent in

adults until recent evidence obtained using 18-fluorodeoxyglucose (18-FDG)

positron emission tomography/computed tomography. It seems to play a role in

whole body metabolism, but it has not been evaluated in underweight conditions,

such as in young females with constitutional leanness (CL) or anorexia nervosa

(AN).

SUBJECTS AND METHODS: Thirty-eight subjects were evaluated from October 2011 to

March 2012 : 7 CL (21.7 ± 3.6 y, body mass index [bMI] 16.2 ± 1.0 kg/m(2)), 7 AN

(23.4 ± 4.5 y, BMI 15.5 ± 0.8), 3 of the 7 AN after stable refeeding (R-AN, 21.3

± 1.5 y, BMI 18.8 ± 1.1), and 24 normal weight (NW) women (25.6 ± 3.9 y, BMI 22.2

± 1.5). Fasting resting metabolic rate and respiratory quotient were measured by

indirect calorimetry, body composition by bioimpedentiometry (only in CL, AN, and

refed AN), and BAT activity by 18-FDG positron emission tomography/computed

tomography scan, all in standardized conditions.

RESULTS: All CL (100%), none of the AN and refed AN (0%), and 3 of the 24 NW

(12%) subjects showed FDG uptake. Average FDG maximum standardized uptake value

was 11.4 + 6.7 g/mL in CL and 5.5 ± 1.2 g/mL (min 3.7, max 8.3) in the 3 NW

subjects. In CL, the maximum standardized uptake value was directly correlated to

resting metabolic rate, corrected for fat-free mass, and inversely correlated

with respiratory quotient.

CONCLUSION: BAT activity has been shown in CL in resting thermoneutral conditions

and may exert a role against adipose tissue deposition.

 

PMID: 23393181

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66 sounds like normal to my thinking and body, although I tend to overdress. So what are we talking about in practical terms here? I drive to work and back with little to no heat. I am shivering at times and that amounts to about an hour a day. For some reason, probably conditioning, I kind of like it during my drives- it's like caffeine lol. Really!

 

So is an hour of cold/ mild shivering daily going to have any positive impact?

Edited by mikeccolella

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Hi Mike,

 

Many of the human brown fat experiments are done at temperatures in the low- to mid-60s F.

 

For example, this study [1], put healthy young men in a cooling suit set to 64F for 3 hours, and observed an 80% increase in total energy expenditure (about an extra 250kcal burned) averaged across subjects, due largely to activation of BAT.

 

Here are an interesting passage from the full text of this paper:

 

The wide interindividual differences in detectable BAT volume of activity (from to 31 to 329 ml) observed in young healthy men in the present study suggests that unknown factors may modulate BAT volume and thermogenic capacity in addition to age, sex, body mass index, and diabetes (24). 

 

So the amount of BAT varied by a factor of 10 among these young male subjects! Pretty dramatic. Part of the variation is probably genetic, and part of it may be differences in prior cold exposure.

 

Furthermore, we found a significant inverse relationship between BAT volume of activity and shivering.

 

So while it's hard to measure BAT directly (since it requires a PET scan or autopsy...), is appears that the temperature at which you start shivering might serve as a rough gauge of how much BAT you have.

 

How low can you go? :-)

 

--Dean

 

-------------

[1] J Clin Invest. 2012 Feb;122(2):545-52. doi: 10.1172/JCI60433. Epub 2012 Jan 24.

Brown adipose tissue oxidative metabolism contributes to energy expenditure
during acute cold exposure in humans.

Ouellet V(1), Labbé SM, Blondin DP, Phoenix S, Guérin B, Haman F, Turcotte EE,
Richard D, Carpentier AC.

Author information:
(1)Centre de recherche de l’Institut universitaire de cardiologie et de
pneumologie de Québec, Université Laval, Quebec City, Quebec, Canada.

 

Free full text: http://www.jci.org/articles/view/60433?key=5e3684aee3d55b74adc8

Comment in
J Clin Invest. 2012 Feb;122(2):486-9.

Brown adipose tissue (BAT) is vital for proper thermogenesis during cold exposure
in rodents, but until recently its presence in adult humans and its contribution
to human metabolism were thought to be minimal or insignificant. Recent studies
using PET with 18F-fluorodeoxyglucose (18FDG) have shown the presence of BAT in
adult humans. However, whether BAT contributes to cold-induced nonshivering
thermogenesis in humans has not been proven. Using PET with 11C-acetate, 18FDG,
and 18F-fluoro-thiaheptadecanoic acid (18FTHA), a fatty acid tracer, we have
quantified BAT oxidative metabolism and glucose and nonesterified fatty acid
(NEFA) turnover in 6 healthy men under controlled cold exposure conditions. All
subjects displayed substantial NEFA and glucose uptake upon cold exposure.
Furthermore, we demonstrated cold-induced activation of oxidative metabolism in
BAT, but not in adjoining skeletal muscles and subcutaneous adipose tissue. This
activation was associated with an increase in total energy expenditure. We found
an inverse relationship between BAT activity and shivering. We also observed an
increase in BAT radio density upon cold exposure, indicating reduced BAT
triglyceride content. In sum, our study provides evidence that BAT acts as a
nonshivering thermogenesis effector in humans.

PMCID: PMC3266793
PMID: 22269323

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To even more thoroughly answer Mike's question about what it takes to activate BAT, below is the table from the full text of review article [1] showing the various cooling protocols used in human studies of BAT activity. 

 

For those of us who are Celcius impaired, here is a conversion for the various temperatures used:

 

°C     °F

16     61

17     63

18     64

19     66

20     68

 

The studies that were most effective at eliciting BAT activity in people used temperatures between 61 and 64°F (16-18 °C).

 

--Dean

 

 

F1.large.jpg?width=800&height=600&carous

 

 
-----------------
[1] Am J Physiol Regul Integr Comp Physiol. 2014 Jul 15;307(2):R103-13.
 
Cold-activated brown adipose tissue in human adults: methodological issues.
 
van der Lans AA, Wierts R, Vosselman MJ, Schrauwen P, Brans B, van Marken
Lichtenbelt WD.
 
 
The relevance of functional brown adipose tissue (BAT) depots in human adults was
undisputedly proven approximately seven years ago. Here we give an overview of
all dedicated studies that were published on cold-induced BAT activity in adult
humans that appeared since then. Different cooling protocols and imaging
techniques to determine BAT activity are reviewed. BAT activation can be achieved
by means of air- or water-cooling protocols. The most promising approach is
individualized cooling, during which subjects are studied at the lowest
temperature for nonshivering condition, probably revealing maximal nonshivering
thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using
the individualized cooling protocol. Currently, the most widely used technique to
study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose
([18F]FDG)-positron emission tomography/computed tomography (PET/CT) imaging.
Dynamic imaging provides quantitative information about glucose uptake rates,
whereas static imaging reflects overall BAT glucose uptake, localization, and
distribution. In general, standardized uptake values (SUV) are used to quantify
BAT activity. An accurate determination of total BAT volume is hampered by the
limited spatial resolution of the PET image, leading to spillover. Different
research groups use different SUV threshold values, which make it difficult to
directly compare BAT activity levels between studies. Another issue is the
comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with
baseline values. This comparison can be performed by using the “fixed volume”
methodology. Finally, the potential use of other relatively noninvasive methods
to quantify BAT, like magnetic resonance imaging or thermography, is discussed.
 
PMID: 24871967

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I'm not a bear for punishment and like to be comfortable.  But at the end of a day I take off my sweater and open top shirt buttons to prepare for sleep.  I enjoy sleeping in a cool room and need to have my hands and especially feet warm to go to sleep on average four times per night.

 

They say when doing such things as driving a vehicle, keep your feet coo and head warm.  For going to sleep, which you do not wnat to do when driving, do the opposite.

 

http://time.com/3602415/sleep-problems-room-temperature/

 

"Healthy men who spent a month sleeping in a cool (but not cold) 66-degree room increased their stores of metabolically active brown fat ... “Brown fat” may not sound very desirable, but it actually helps your body burn calories and dispose of excess blood sugar, he explains.?"

 

"In Celi’s brown fat experiment, the men slept under thin sheets. ... while the cold may be good for your metabolism and brown fat stores, you may be paying for those benefits with a night of fitful sleep."

 

"keeping your skin temperature “perfectly comfortable” is important when it comes to maintaining deep, restful slumber."

 

"the bottom line: keeping your head nice and cool is conducive to good sleep. To achieve that, set your thermostat somewhere around 65 degrees, research suggests. And layer up until you feel the Sandman creep closer."

 

 

http://healthland.time.com/2011/06/17/tip-for-insomniacs-cool-your-head-to-fall-asleep/

 

"Researchers from the University of Pittsburgh School of Medicine"

 

"When Buysse’s group gave 12 insomniacs a cap to wear that contained circulating water at cool temperatures, they were able to get them to fall asleep almost as easily as people without sleep disorders: using the caps, the insomniacs took about 13 minutes to fall asleep, compared with 16 minutes for the healthy controls, and they slept for 89% of the time they were in bed, which was similar to the amount of time the controls spent asleep."

 

"melatonin, one of the more effective medications to help people sleep, also works in part by lowering body temperature."

 

 

Brown adipose tissue--when it pays to be inefficient.
Celi FS.
N Engl J Med. 2009 Apr 9;360(15):1553-6. doi: 10.1056/NEJMe0900466. No abstract available.
PMID: 19357412 Free PMC Article
 
Figure 1
nihms147035f1.jpg
The Activation of Brown Adipose Tissue

Stimulation of β3-adrenergic receptors leads to the dramatic increase in the intracellular concentration of triiodothyronine (T3) by means of the type 2 5′ deiodinase (D2); T3 in turn stimulates the transcription of uncoupling protein 1 (UCP1), which causes the leakage of protons from the inner membrane of the mitochondria, hence dissipating energy in the form of heat. The abbreviation cAMP denotes cyclic adenosine monophosphate, CRE cAMP response element, T4 thyroxine, and TRE thyroid hormone response element.

 
 
N Engl J Med. 2009 Apr 9;360(15):1518-25. doi: 10.1056/NEJMoa0808949.
Functional brown adipose tissue in healthy adults.
Virtanen KA1, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerbäck S, Nuutila P.
PMID: 19357407
 
Abstract
 
Using positron-emission tomography (PET), we found that cold-induced glucose uptake was increased by a factor of 15 in paracervical and supraclavicular adipose tissue in five healthy subjects. We obtained biopsy specimens of this tissue from the first three consecutive subjects and documented messenger RNA (mRNA) and protein levels of the brown-adipocyte marker, uncoupling protein 1 (UCP1). Together with morphologic assessment, which showed numerous multilocular, intracellular lipid droplets, and with the results of biochemical analysis, these findings document the presence of substantial amounts of metabolically active brown adipose tissue in healthy adult humans.
 
 
N Engl J Med. 2009 Apr 9;360(15):1509-17. doi: 10.1056/NEJMoa0810780.
Identification and importance of brown adipose tissue in adult humans.
Cypess AM1, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR.
PMID: 19357406 Free PMC Article
 
Abstract
BACKGROUND:
 
Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans.
 
METHODS:
 
We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery.
 
RESULTS:
 
Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007).
 
CONCLUSIONS:
 
Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.
 
 
N Engl J Med. 2009 Apr 9;360(15):1500-8. doi: 10.1056/NEJMoa0808718.
Cold-activated brown adipose tissue in healthy men.
van Marken Lichtenbelt WD1, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ.
PMID: 19357405 Free full text
 
Abstract
 
BACKGROUND:
 
Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism.
 
METHODS:
 
We studied 24 healthy men--10 who were lean (body-mass index [bMI] [the weight in kilograms divided by the square of the height in meters], < 25) and 14 who were overweight or obese (BMI, > or = 25)--under thermoneutral conditions (22 degrees C) and during mild cold exposure (16 degrees C). Putative brown-adipose-tissue activity was determined with the use of integrated (18)F-fluorodeoxyglucose positron-emission tomography and computed tomography. Body composition and energy expenditure were measured with the use of dual-energy x-ray absorptiometry and indirect calorimetry.
 
RESULTS:
 
Brown-adipose-tissue activity was observed in 23 of the 24 subjects (96%) during cold exposure but not under thermoneutral conditions. The activity was significantly lower in the overweight or obese subjects than in the lean subjects (P=0.007). BMI and percentage of body fat both had significant negative correlations with brown adipose tissue, whereas resting metabolic rate had a significant positive correlation.
 
CONCLUSIONS:
 
The percentage of young men with brown adipose tissue is high, but its activity is reduced in men who are overweight or obese. Brown adipose tissue may be metabolically important in men, and the fact that it is reduced yet present in most overweight or obese subjects may make it a target for the treatment of obesity.

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Wow, very cool thread. The sleep angle is of particular interest to me. I'd already lowered my bedroom from 23° to 20°, without noticing an effect on sleep, but after reading the above, I think I'll push it down further, and see what happens. Even if I don't sleep better, it sounds like I might end up improving my health.
 
Dean, judging by the footwear it looks like your daughter is doing ballet in the snow!
 
Zeta

 

P.S. Only now noticed my unintentional pun.

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Good eyes Zeta,

 

Yes, my daughter is a dancer (mostly ballet) and wanted some dramatic poses in snow for her portfolio. That is just one of many she and I took yesterday, and one of the less aerobatic ones.

 

I too sleep with very light covers in a cool room (~18C = 64F). I find I've gotten used to it and seem to be sleeping quite soundly lately. But it does take some acclimatization / getting used to.

 

--Dean

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"Bait-and-switch", "acclimatization"? This is clearly our day for puns!

 

Back to the cool thread: I may not feel comfortable enough if my body is much colder/exposed. If I'm not, I might try to fashion a head-cooling cap of some kind, sort of like the cooling vest, but for my head. I see from a quick Google search that such things exist and can actually be purchased. (What can't, these days!)

 

Zeta

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Zeta,

 

"Bait-and-switch", "acclimatization"? This is clearly our day for puns!

 

I actually didn't intend to use acclimatization as a pun in the context of sleeping in cool conditions. I meant it to suggest literal adaptation to the cold - via building up more BAT!

 

But for "bait-and-switch" comment on the Fish & PCBs thread, that was was definitely me trying to be clever :-).

 

Cooling headgear might do the trick, but if you want to cool your head and keep your body warm(er), why not just turn down the thermostat and use more covers to compensate, but leave your head exposed? That has the added benefit of saving on your heating bill in the process. Are you in a warm climate, or are there others in your household whose comfort you need to consider?

 

--Dean

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Hi ALL!

 

As I've indicated before, I consider this a very interesting topic -- I hope that there will be a talk at CR IX on the effects of cold exposure, and perhaps also on the very interesting effects of the protein FGF21.

 

  -- Saul

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Why not just turn down the thermostat and use more covers to compensate, but leave your head exposed?

 

The heating system in my building (apt. complex) is such that there's no way to lower the temperature in my bedroom below around 16-17° or so. And once summer comes, the head cooler will of course be far more efficient.

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I've been doing quite a lot of self experimentation lately with cold exposure.  I've also reconfigured the techkewl vest by putting 2 of the PCM packs over my shoulders like football shoulder pads, while the other two cover my ribs (Dean you asked about this earlier - the cooling packs go from the top of the logo all the way to the bottom of the vest and almost as wide as the vest (you can see the seams if you look closely):

techkewlovershoulder.jpg

 

A vest more specifically designed to target BAT might be a better option.

Like others, I also have a pretty long commute, so I've been trying cold exposure then as well, down to the goose bump level, tee shirt all week, no heat or coats.  Its really interesting how quickly you can become cold adapted.  My tolerance for cold has greatly increased during my experimentation.  I am also certain I have activated my BAT.  I think this is probably even more obvious to CR practitioners.  I kept my diet, caloric intake, and exercise the same as it has been for a long time, but the cold exposure has caused me to become ravenously hungry during my normal evening fast period.  Last night I broke the usual fast and ended up eating a tomato, handful of walnuts, an entire pint of blueberries, a clementine, and a pickle (odd that I had a strong craving for pickles like a pregnant woman).  Despite the extra eating, I have lost weight (not something I was shooting for).  So all of this is very interesting, but its also going to cost me $ and some would argue, waste food.  I guess if there are significant health/longevity benefits it might be worth it.  I tried to amp up my regular meals more today, which helped although I'm still hungry this evening as I chill, haha.  I'll have to compensate even more for the extra calories burned by BAT when I'm doing this.

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Gordo,

Thanks for the update. Pretty clever of you to shift the cooling packs to the shoulders. I'm not surprised about increased hunger and the extra calorie needs. It's amazing how much extra energy a little brown fat can burn when you are cold. 

 

--Dean

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All,

 

Saul wrote:

As I've indicated before, I consider this a very interesting topic -- I hope that there will be a talk at CR IX on the effects of cold exposure, and perhaps also on the very interesting effects of the protein FGF21.

 

I don't think I've pointed to all the evidence that exercise is yet one more way to increase brown fat. Here is a good paper [1] (and press release) on it. This is the graphical abstract from the paper:

 

Image%20%5B7%5D.png

 

So from the full text, and from this diagram, it appears that non-shivering thermogenesis (like several of us are experimenting with via cold exposure) increases FGF21, which in turn causes an increase in brown fat levels. Exercise appears to mimic shivering thermogenesis, which creates more brown fat via another pathway, specifically by increasing another hormone, Irisin, which turns white fat to brown fat. So for those following along, here is the latest list of things that appear to increase and/or activate brown fat:

  • Cold exposure - by far the best BAT activator
  • Metformin
  • Green Tea
  • Caffeine
  • Capsaicin
  • Low protein diet
  • Exercise

I'll note once again that all of these are thought to be health-promoting and/or life-extending. Could the fact that they all increase levels of brown fat have something to do with it? I seems like a strong possibility....

 

--Dean

 

-------------

[1] Cell Metab. 2014 Feb 4;19(2):302-9. doi: 10.1016/j.cmet.2013.12.017.

Irisin and FGF21 are cold-induced endocrine activators of brown fat function in
humans.

Lee P(1), Linderman JD(1), Smith S(1), Brychta RJ(1), Wang J(1), Idelson C(1),
Perron RM(1), Werner CD(1), Phan GQ(2), Kammula US(2), Kebebew E(3), Pacak K(4),
Chen KY(1), Celi FS(5).

Full text: http://dx.doi.org.sci-hub.io/10.1016/j.cmet.2013.12.017

Rediscovery of cold-activated brown adipose tissue (BAT) in humans has boosted
research interest in identifying BAT activators for metabolic benefits. Of
particular interest are cytokines capable of fat browning. Irisin, derived from
FNDC5, is an exercise-induced myokine that drives brown-fat-like thermogenesis in
murine white fat. Here we explored whether cold exposure is an afferent signal
for irisin secretion in humans and compared it with FGF21, a brown adipokine in
rodents. Cold exposure increased circulating irisin and FGF21. We found an
induction of irisin secretion proportional to shivering intensity, in magnitude
similar to exercise-stimulated secretion. FNDC5 and/or FGF21 treatment
upregulated human adipocyte brown fat gene/protein expression and thermogenesis
in a depot-specific manner. These results suggest exercise-induced irisin
secretion could have evolved from shivering-related muscle contraction, serving
to augment brown fat thermogenesis in concert with FGF21. Irisin-mediated
muscle-adipose crosstalk may represent a thermogenic, cold-activated endocrine
axis that is exploitable in obesity therapeutics development.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID: 24506871

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All,

 

As observed in the previous post, non-shivering thermogenesis appears to upregulate FGF21, which boosts levels of brown fat. We also saw earlier in this thread (in this post), perhaps not coincidently as I've argued, that elevated FGF21 is associated with lifespan extension, at least in mice (PMID 23066506).

 

Now I've come across an interesting fact about curcumin, which nearly everyone believes to be health promoting, except apparently Michael who seems (seemed?) to think evidence in favor of curcumin to be rank nonsense :-).

 

Study [1] found that curcumin, like cold exposure, elevates the apparent lifespan-extending protein FGF21, both in vitro in liver cells from normal C57BL/6 mice and in vivo in a mice model of insulin resistance. Since we saw above (PMID 24506871) that FGF21 boosts brown fat levels, now it appears we can add curcumin to the list of brown fat increasing/activating interventions (i.e. curcumin -> increased FGF21 -> increased brown fat). So here is the latest full list of brown fat inducers:

  • Cold exposure - by far the best BAT inducer/activator
  • Metformin
  • Green Tea
  • Caffeine
  • Capsaicin
  • Curcumin
  • Low protein diet
  • Exercise

--Dean

 

 

----------

[1] J Nutr. 2015 Oct;145(10):2300-7. doi: 10.3945/jn.115.216853. Epub 2015 Sep 2.

Short-Term Curcumin Gavage Sensitizes Insulin Signaling in Dexamethasone-Treated
C57BL/6 Mice.

Tian L(1), Zeng K(2), Shao W(3), Yang BB(4), Fantus IG(5), Weng J(6), Jin T(7).

BACKGROUND: Long-term dietary curcumin (>12 wk) improves metabolic homeostasis in
obese mice by sensitizing insulin signaling and reducing hepatic gluconeogenesis.
Whether these occur only secondary to its chronic anti-inflammatory and
antioxidative functions is unknown.
OBJECTIVE: In this study, we assessed the insulin sensitization effect of
short-term curcumin gavage in a rapid dexamethasone-induced insulin resistance
mouse model, in which the chronic anti-inflammatory function is eliminated.
METHODS: Six-week-old male C57BL/6 mice received an intraperitoneal injection of
dexamethasone (100 mg/kg body weight) or phosphate-buffered saline every day for
5 d, with or without simultaneous curcumin gavage (500 mg/kg body weight). On day
7, insulin tolerance tests were performed. After a booster dexamethasone
injection and curcumin gavage on day 8, blood glucose and insulin concentrations
were measured. Liver tissues were collected on day 10 for quantitative polymerase
chain reaction and Western blotting to assess gluconeogenic gene expression,
insulin signaling, and the expression of fibroblast growth factor 21 (FGF21).
Primary hepatocytes from separate, untreated C57BL/6 mice were used for testing
the in vitro effect of curcumin treatment.
RESULTS: Dexamethasone injection impaired insulin tolerance (P < 0.05) and
elevated ambient plasma insulin concentrations by ~2.7-fold (P < 0.01).
Concomitant curcumin administration improved insulin sensitivity and reduced
hepatic gluconeogenic gene expression. The insulin sensitization effect of
curcumin was demonstrated by increased stimulation of S473 phosphorylation of
protein kinase B (P < 0.01) in the dexamethasone-treated mouse liver, as well as
the repression of glucose production in primary hepatocytes (P < 0.001). Finally,
curcumin gavage increased FGF21 expression by 2.1-fold in the mouse liver (P <
0.05) and curcumin treatment increased FGF21 expression in primary hepatocytes.
CONCLUSION: These observations suggest that the early beneficial effect of
curcumin intervention in dexamethasone-treated mice is the sensitization of
insulin signaling, involving the stimulation of FGF21 production, a known insulin
sensitizer.

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