Thursday, January 17, 2013

Tapping into Brown Fat?

One of the impending health threats in the future is the increasing rate of obesity in the United States as well as the rest of the world. While the rate of obesity has ebbed slightly in the last year the number of obese individuals is still increasing in absolute terms due to population growth and greater access to food choices in developing countries. Numerous rationalities have been given to explain this increase ranging from too much food and not enough exercise to changing bacterial concentrations in the intestinal tract. Certainty the type of bacteria in one’s intestine affects the ability to process fats, carbohydrates and proteins from various food sources.1,2 However, despite the claims of numerous food products and their positive probiotic messages there is no proof that any of these products have a net positive benefit in managing weight. Gastro bypass surgery has a mixed history of success and for some patients has serious side effects. Therefore, the only truly viable proven method for consistently controlling weight is physical exercise and an appropriate diet.

Unfortunately numerous individuals do not enjoy exercise, so it would behoove many to develop a methodology that increased its effectiveness. Numerous “entrepreneurs” have made attempts at “increasing” exercise effectiveness with various pieces of equipment or programs, yet almost all of them are questionable in their viability. What needs to be addressed is a biochemical methodology that has influence in a majority of individuals. One strategy may be to tap into the unique properties of brown adipose tissue (a.k.a. brown fat).

There are two key elements to the fat burning capacity of brown fat. First, brown fat have multiple mitochondria versus the single mitochondria possessed by white fat which allows for greater rates of metabolism along with an increased lipid concentration. Also brown fat releases norepinephrine which reacts with lipases to breakdown fat into triglycerides and later to glycerol and non-esterified fatty acids and finally CO2 and water acting in as a positive feedback mechanism, in a sense.3,4 Second, brown fat contains uncoupling protein 1 (UCP-1).3 UCP-1 is responsible for dissipating energy, which leads to the decoupling of ATP production and mitochondrial respiration.3 Basically UCP-1 returns protons after they have been pumped out of the mitochondria by the electron transport chain where the protons are released as heat instead of producing energy.

The shiver response involves the activation of the primary motor in the posterior hypothalamus when inhibitory signals from the anterior hypothalamic-preoptic are overridden by temperature dependent sensory information from the skin and spinal cord.5 In response to this sensory information muscles begin to vibrate (i.e. shake) resulting in the production of heat as a byproduct to the activity. The key physiological role brown fat plays in mammals, especially those who do not have a shiver response, is it operates as a thermogenic organ where mitochondrial respiration is uncoupled from ATP production.4 The shiver response relies on volume of produced heat versus heat per unit, without the ability of volume brown fat augments the heat per unit amount, due to the lack of ATP production instead focusing on heat alone, in an attempt to compensate.

For a number of years it was thought that humans lost their brown fat after infancy, but numerous PET and CT studies have confirmed that adults do have concentrations of brown fat most notably in the supraclavicular area.6,7 Therefore, one could increase metabolic activity by activating brown fat in some individuals. It is important to note that global patterns of obesity are not viewed as complete enough to determine whether obesity rates are higher in warmer countries versus colder countries to provide a form of empirical support for increased brown fat despots relative to surface temperature; however, any correlation due to ambient temperatures would probably be weak because of adaptation of the shiver response.

While cold is the most common method for activating brown fat, it is not the only method to accelerate the mitochondrial activity of brown fat. Catecholamines have a similar activation effect largely because of their involvement in the fight or flight response. It makes sense that the more efficient energy producers in the body would be activated when facing a stressful life-or-death situation. Unfortunately beta blockers, which are commonly used to control high blood pressure, a common symptom in obese individuals, block catecholamines and reduce the probability of activating brown fat through catecholamine interaction. Epinephrine and caffeine also show promise in increasing brown fat activation, but epinephrine derived from drugs have too many side effects and caffeine consumption could result in too many additional calories counteracting the increase in brown fat activation.

As noted earlier norepinephrine appears especially important in triggering additional brown fat activation resulting in an increased rate of oxygen consumption and fatty acid release. Thus, the consumption of foods high in norepinephrine precursors could aid in increasing brown fat efficiency probability. Another advantage to utilizing brown fat as an augmented element to increased metabolic activity is that its decoupled nature from ATP production should result in limited to no additional oxidative free radical production from its specific mitochondria. Therefore, activation of this methodology should not increase possibilities for cellular damage and increase the rate of aging in a given subject.

Still, many questions remain before those next steps can be taken. For one thing, why is it that obese people tend to have very little brown fat compared with lean people? One possibility is that as brown fat can “eat” white fat, brown fat could also become white fat. If brown fat is not utilized it may experience apoptotic consequences. An aspect of this die-off could occur because brown fat chief role is its thermogenesis response, but more obese individuals have greater thermal insulation due to their fat content, thus have more difficulty initiating brown fat activation due to external temperature changes and competition with the shiver response.

It is also probably worth remembering how researchers discovered that adults retained stores of brown fat in the first place: they were studying head and neck scans of patients with cancer and noticed that in addition to tumor sites, certain parts of the neck also showed higher rates of glucose consumption.8 This additional rate of glucose consumption was theoretically driven by additional brown fat because brown fat appeared to be at greater concentrations in cancer patients versus individuals without cancer/tumors.8 One explanation for this additional brown fat could be that the excess energy requirements for cells that have shed their growth limitations demand conversion of white fat into brown fat through the methodology discussed above. If this theory is accurate then brown fat follows tumor development not that other way around, thus increasing brown fat stores will not increase the probability that an individual develops cancer.

While some individuals believe that one way to utilize brown fat is to develop a “cold sauna” that individuals can simply sit in, wouldn’t it be better to combine brown fat activation with white fat “activation”? There still is limited information on what type of exposure regiment is optimal for brown fat activation. For example is it better to be exposed to high intensity cold at low volume (-50 degrees F for 30 seconds) or low intensity cold at high volume (20 degrees F for 5 minutes)? Note that brown fat activates as long as the temperature is cold enough whether it is acute cold or eventual chronic cold; however, prolonged exposure to certain cold conditions can produce negative results for exposed skin, so determining a differentiated methodology would be advisable. Also gyms or cold saunas would have to set up a stepwise exposure protocol allowing users to move gradually from initial temperatures to final temperatures because a near instant temperature change from say 70 degrees F to 0 degrees F would be detrimental to the body, especially those with health problems.

Outside this methodology one could have short-term cold exposure (40 degrees F for 10 minutes) and then engage in cardiovascular exercise. The cold exposure will stimulate the brown fat with the later exercise continuing the brown fat stimulation and initiating some level of white fat loss. Another possibility would be the increased rate of norepinephrine release increasing the probability of white fat becoming brown fat due to increased activation rates along with the release of norepinephrine possibly reducing pain associated with exercising (acting as a biological pain killer). Overall with available brown fat stores still in adults, no risk for increased cancer development and the ability to produce more brown fat when routinely activated it seems that gyms should think about installing “cold saunas” not necessarily for solitary fat burning, but instead as a preparation element for a more complete calorie and fat burning workout.


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Citations:

1. Backhed, F, et, Al. “The gut microbiota as an environmental factor that regulates fat storage.” PNAS. 2004. 101(44): 15718–23.

2. Cani, P, et, Al. “Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding.” Pathologie Biologie. 2008. 56:305–309.

3. van Marken Lichtenbelt, W, et Al. “Cold-activated brown adipose tissue in healthy men.” The New England Journal of Medicine. 2009. 360:1500-08.

4. Lowell, B, and Spiegelman, B. “Towards a molecular understanding of adaptive thermogenesis.” Nature. 2000. 404:652-60.

5. http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=& term=Shivering

6. Hany, T, et Al. “Brown adipose tissue: a factor to consider in symmetrical tracer uptake in the neck and upper chest region.” Eur J. Nucl Med. Mol Imaging. 2002. 29:1393-8.

7. Nedergaard, J, Bengtsson, T, and Cannon, B. “Unexpected evidence for active brown
adipose tissue in adult humans.” Am. J. Physiol. Endocrinol. Metab. 2007. 293:E444-
E452.

8. Rousseau, C, et Al. “Brown fat in breast cancer patients: analysis of serial (18)F-FDG PET/CT scans.” Eur J. Nucl Med. Mol Imaging. 2006. 33:785-91.

1 comment:

  1. Great post!

    You should take a look at what Joslin Research Center (Harvard Medical School) has found with regard to Brown Adipose Tissue stimulation. They found using a cooling vest set to 14°C temperature activated brown adipose tissue. Other research has tried to mimic this study with even colder temperatures but could not find any consistent results as all the patients were shivering.

    We at TechNiche International have developed a Cooling Vest that maintains the 14°C temperature for 2-3 hours while stimulating all major depots of brown fat in the body. Our vests branded KewlFit, can also be worn as a performance aid as we have many world class athletes wearing it to pre, post and during exercise cool.

    Take a look at our information website www.kewlfit.com

    Thanks and we look forward to hearing from you.

    Regards,
    KewlFit
    info@kewlfit.com

    ReplyDelete