The Fat That Can Make You Thin
Introduction
If you have come across the superhuman feats of the “Ice-man” Wim Hof you may also have heard how brown fat cells may be partially responsible.
So what is brown fat?
To help answer this question I found a recent (2015) open-access review by Sidossis and Kajmura [1]which you can download here.
There is also a review from 2013 by Harms and Seale [3] which has some fantastic diagrams by Debbie Maizels which you can download here.
It may be a bit difficult to follow for those who are not used to medical review papers so I have attempted to summarise and explain the main research that they cover.
I hope you find it useful:
Brown Adipose Tissue vs. White Adipose Tissue
Before we start a few definitions: Adipose is just another name for fat and a tissue is a collection of cells.
So brown adipose tissue (which gets abbreviated to BAT) just means a collection of brown fat cells.
Most of us are familiar with the normal kind of fat cells — known as white adipose tissue (WAT). These are used as an energy store.
In recent years you may have heard news stories about a different type of fat cell known as brown fat or brown adipose tissue (BAT). — So what is it?
According to Siddosis et al [1]:
“Brown adipose tissue (BAT) evolved as a natural defense system against hypothermia in mammals.” [1]
“BAT is composed of a specialized form of adipocytes that contain numerous lipid droplets (multilocular lipids) and large mitochondria.” [1]
Translation: adipocytes = fat cells; lipids = fats; multilocular = multiple small compartments; mitochondria = energy producing structures.
BAT expresses high levels of a gene called UCP-1. These cells also have more mitochondria (the energy factories of the cell) than regular white fat cells and as a result burn large amounts of energy as opposed to simply storing it:
“Activation of UCP1 in response to cold exposure or food intake results in increased glucose and free fatty acid (FFA) oxidation in order to sustain high levels of uncoupled respiration within BAT, that is, mitochondrial respiration that leads to heat generation.” [1]
Translation: ‘respiration’ here refers to cellular respiration which is energy production in simple terms, ‘uncoupling’ is a method which favours heat production.
Previously it was assumed that brown fat only exists in human infants but growing research is showing that it is maintained into adulthood.
“Now a number of prospective studies have reported that many, if not all, adult humans possess metabolically active BAT, and its mass shows an inverse correlation with BMI and adiposity.” [1]
So those people who have larger amounts of brown fat deposits tend to be leaner.
BAT deposits are mainly found around the neck and shoulder regions in humans as shown in the diagram above.
Different individuals have different amounts and it seems that you are born with a certain amount which is maximal during infancy and that level decreases due to normal cell death/turnover throughout life.
Beige Fat vs Brown Fat
In recent years another type of fat cell has also been studied. This is known as beige fat.
Unlike brown fat, beige fat cells seem to arise within deposits of white fat/WAT.
Like brown fat they also have larger numbers of mitochondria, express the UCP-1 gene and similarly increased metabolic activity.
The main difference with beige fat cells compared to brown fat is that their metabolic activity is more variable in response to environmental conditions.
Although the exact lineage is unknown, it is believed that these cells are derived from a different cell line than brown cells and they are more closely related to white fat cells (see diagram).
Beige cells appear to start off much like other white fat cells with low metabolic activity and UCP-1 expression.
In response to certain environmental stimulants these inactive beige cells then become activated — increasing their mitochondria and UCP-1 expression, raising their metabolic rate and hence their fat burning activity.
This has been termed WAT “browning” and has been demonstrated in mice — regular exposure to cold “activates” these precursor cells to become beige cells.
Removing the cold exposure and simulating a warm climate restores them to a pre-”beige” state.
Therefore unlike brown cells, beige cells can return to a white cell-like level of energy expenditure as a result of environmental factors.
Brown fat cells and normal white fat cells do not appear to be able to do this.
Why is this important?
Hardly a day goes by that we do not hear new stories about the epidemic of obesity and type 2 diabetes that we are suffering in modern times.
Brown and beige fat cells may provide an extra tool to help fight these conditions.
Multiple genes have been identified that seem to promote BAT/beige cell activity.
If you are interested there is an extensive table with a list (Table 1) in the paper by Harms and Seale [3].
Certain natural and artificial chemical compounds may also be able to do the same and this is an expanding area of research.
In theory it should be possible to develop drugs that can mimic the activity of these genes and compounds in order to stimulate WAT “browning” — hopefully without any serious side effects.
More exciting in the meantime is that controlled exposure to cold conditions seems to increase levels of beige fat.
— A process that may explain the ability of people like Wim Hof to progressively alter their ability to withstand cold conditions which would induce hypothermia in untrained subjects.
Factors which seem to encourage “browning” of fat cells
Multiple factors have been identified. Some obvious and some not so obvious.
- Controlled Cold Exposure — this seems to stimulate activation of UCP-1 and production of stress hormones in a way that is actually beneficial vs. regular everyday stress.
- Environmental Enrichment — It appears keeping your mind and hence brain stimulated leads to production of BDNF (brain derived neurotrophic factor) and this also seems to promote browning of WAT.
- Exercise — has been shown to induce WAT browning and increase energy expenditure via this pathway. A number of mechanisms have been implicated which are beyond the scope of this article.
- Cancer — the weight loss in cancers is due to multiple factors but one of them appears to be increased cell browning caused by tumour released factors e.g. IL6.
- Various natural hormones, metabolites and also transcriptional mediators — too many to list here but see the review by Sidossis et al for more information. See also the diagram above this text.
Obesity, BAT and Browning of WAT
Obesity seems to be associated with the production of multiple factors which inhibit browning of WAT cells and may also interfere with the functioning of BAT.
One of these is TGF-ß (Transforming growth factor beta) — blockade of which can increase browning/energy expenditure.
Previous research by Kozak et al [1], suggests that genetic propensity to obesity in rodents at least is:
“linked to UCP1 expression in WAT (i.e., beige adipocytes) but not with that in interscapular BAT (i.e., classical brown adipocytes), highlighting the biological significance of beige adipocytes in the propensity to obesity.” [1]
In humans there is less evidence and research is still ongoing.
Certain polymorphisms (different versions) of the UCP1 gene and ß3-adrenergic receptor genes seem to reduce base energy expenditure and resistance to cold.
EHMT1 (Euchromatic histone-lysine N-methyltransferase) is a gene that has been implicated in lowered brown and beige adipocyte levels.
People who have a “haploinsufficiency” (basically they only have a single functional copy of the gene) have a much higher probability of developing obesity (~50%) versus the rest of the population.
These are not the only genetic factors that have been studied and it is likely that as research proceeds we will find more and more examples of these sorts of associations.
Currently a lot of the data applies to rodent models and it will take time as well as money to see how far this genetic data translates to humans.
BAT/Beige Fat and Glucose
BAT and beige fat are able to reduce blood levels of both triglycerides (fat components) and glucose (the main blood sugar) circulating in the blood.
This makes them an exciting area for research in treating type 2 diabetes (in addition to simple obesity):
“An emerging idea is that generating a new “metabolic sink” for glucose, triglycerides, and possibly other metabolites through promoting beige adipocyte development can lead to an improvement in systemic glucose and lipid homeostasis, in addition to an increase in whole-body energy expenditure.” [1]
“Cold exposure significantly increases glucose disposal in BAT but not in other tissues. Obese individuals seem to exhibit a less pronounced response.” [1]
This would suggest less BAT activity in obese people.
Another recent finding shows that those with higher BAT activity have lower HbA1c (a long term glucose measure) in addition to lower total and LDL cholesterol (the bad kind).
Although these responses are less pronounced in obese individuals they may still be amenable to improvement using techniques like cold exposure or indeed drug based intervention.
Some people have suggested that in addition to our more sedentary lifestyles and dietary changes, the lack of exposure to cold (e.g. from central heating) may also be a contributory factor to obesity and type 2 diabetes.
-Something which may result in less BAT/beige cell activity.
Conclusion
It might be some time before we get (safe) drugs that can increase BAT activity but it seems that exercise and controlled cold exposure (done safely) may be ways to kickstart the process now.
N.B. do not experiment with cold exposure without expert advice as it can be extremely dangerous if done incorrectly.
I myself am looking into the cold exposure side of things to help try to deal with my own obesity problem!
I will let you know of my experiences — assuming I can manage to cope with it.
Finally, I hope you have found this summary useful.
I have tried to translate and explain the most important points of the papers and I hope I have succeeded in this regard.
It is very easy to miss certain points and assume that people understand them so please let me know if you feel something is unclear or not easy to understand.
References
- Sidossis, Labros, and Shingo Kajimura. 2015. “Brown and Beige Fat in Humans: Thermogenic Adipocytes That Control Energy and Glucose Homeostasis.” The Journal of Clinical Investigation 125 (2): 478–86.
- Cypess, Aaron M., and C. Ronald Kahn. 2010. “Brown Fat as a Therapy for Obesity and Diabetes.” Current Opinion in Endocrinology, Diabetes, and Obesity 17 (2): 143–49.
- Harms, Matthew, and Patrick Seale. 2013. “Brown and Beige Fat: Development, Function and Therapeutic Potential.” Nature Medicine 19 (10): 1252–63.
Thank you for reading
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