Turn Unhealthy White Fat to Brown Fat and Burn More Calories and Reduce Excess Body Fat
Brown fat is a vigorous topic of research as obesity continues to burden the United States public health system, and causes considerable distress to individuals across the world.
With the recent classification of obesity as a “disease,” Medicaid and insurance coverage has expanded, which increases the allure for pharmaceutical corporations to develop obesity prevention and treatment options.
Sometimes referred to as “good” fat, brown fat is a tissue that stores fat, but differently from the more typical and familiar white fat. This means that calories from stored fat are much more readily available to brown fat to burn for energy. More exciting is that brown fat burns calories at a much higher rate than white fat because it is packed with mitochondria— the “furnaces” of the cell. It is like having a 12-cylinder monster truck compared to a hybrid subcompact car; you go through a lot more gasoline. Brown fat can burn calories nearly as quickly as lightly exercising muscle. Even more exciting, brown fat has a mechanism that actually “wastes” calories, so the mitochondria do not slow down burning calories (both fat and glucose) when the cell is full of ATP. Just like a gas pump shuts off when your tank is full, cells don’t flood themselves with ATP (the energy molecule)— it is regulated. Brown fat “uncouples” the oxidative metabolism (calorie burning) of fat and sugar through the actions of a class of regulating proteins called uncoupling proteins (UCPs).1 The most relevant to fat burning is UCP1. When the brown fat mitochondria are uncoupled, it is like revving your engine with the clutch pedal pushed to the floor. You are burning fuel, the engine temperature goes up, but you are not going anywhere.
• Burning Calories Without Effort
It was long thought that adult humans did not have any brown fat. Recently, studies have demonstrated that brown fat does in fact exist in adults.2 The holy grail being sought by clinical investigators are ways to both increase the amount of brown fat, and to be able to “turn it on” chemically. Now, there are ways of increasing brown fat activity through changes in behavior or lifestyle. Certainly, one can turn on his/her own brown fat (and possibly increase brown fat mass) by routinely spending time in a cool environment, lightly clothed, just as was done in the imaging studies that confirmed the presence of brown fat in most people. It should be pointed out that it appears that a small percentage of people do not have detectable amounts of brown fat using the techniques reported. Obese people are less capable of activating their brown fat depots as well.3 Nevertheless, government studies have looked at the benefits of reducing the temperature of businesses and residences for combating obesity, insulin resistance and reducing heating costs.4 However, these temperatures may be uncomfortable to many, enough so that they would not implement them, or perhaps dress warmer, defeating the purpose of activating “adaptive thermogenesis.” Also, brown fat tissue can expand (increase in mass) somewhat, but not considerably. How then can this tissue and its ideal properties be utilized to promote weight management?
Brown fat is different from white fat. However, they share a common cellular origin, mesenchymal stem cells; skeletal muscle comes from these cells as well. Though true brown fat cannot be created from white fat, brown-like fat can develop within white fat if the stem cells are subjected to the right conditions and stimuli. Brown-in-white cells are called “brite” or “beige” cells. Beige cells act much like brown fat, being packed with mitochondria and wasting calories as heat; they just aren’t as effective at the process. In fact, brown fat is always ready to “waste” calories, and can do so at a high rate whenever prompted. Beige fat adjusts to the seasons, and can only waste calories if it is convinced it is in a cool to cold environment.5 Summer-like conditions suppress the UCP-1 levels in beige fat almost completely, whereas they can ramp-up 100 times higher if exposed to a very cold environment. Since the temperature of subcutaneous fat does not drop much, as the core temperature prevents it from cold damage, beige fat activity is much less than brown fat, but still adds to calorie wasting significantly.
An exciting discovery was published several years ago demonstrating a messenger signal created in exercising muscle called irisin.6 Irisin is generated when a cellular messenger called PGC1-alpha increases in the muscle cell. Keep this in mind for later. When irisin is released from the muscle membrane, it travels through the bloodstream and activates receptors on cells, including cells in white fat depots. Under the influence of irisin, beige cells can form, which may account for some of the long-term benefits seen with exercise. These include the continued increase in metabolic rate (calorie burning) that occurs for hours after exercise, decreased insulin resistance and triglycerides, etc. Unfortunately, results in human studies have been conflicting and are modest at best.
• Drugs and Supplements That Increase Brown Fat Activity
OK, enough with the hard stuff, dieting and exercise. Is there anything in a pill that can help? There are supplements and drugs that can increase brown and beige fat activity, such as capsaicinoids from cayenne pepper that activate TRPV receptors. Bile acids acting through TGR5 receptors, and berberine via PGC1-alpha, were recently discussed.7,8 Thyroid hormone can increase uncoupling, as well as certain beta-agonist drugs, such as clenbuterol.9
Stimulant fat-loss agents act on beta-adrenergic receptors, of which there are three classes— beta1, beta2 and beta3. Most activate both beta1 and beta2 receptors, which is unfortunate as beta1 stimulation results in rapid heart rate and blood pressure elevation. Beta2 stimulates the metabolism in muscle cells and provides ergogenic benefits; it also has some effect on brown fat. However, beta3 acts on brown and likely beige fat cells to increase “calorie wasting” without any effect on heart rate or blood pressure. A drug used to treat overactive bladder utilizes the beta3 receptor and just recently, a study has been published showing this drug, mirabegron, may be able to provide a weight loss of 10 pounds per year by stimulating brown fat.10 It would require frequent dosing or a sustained-release formulation, and the progress would be slow. Peak effect would be about 200 calories additional wasted through this effect. Sadly, it is likely this drug will show up as an adulterant in a supplement before it is available legitimately for this use.
Briefly, another promising finding was reported in which scientists were able to coerce stem cells from white fat to turn into beige cells using a drug used in the treatment of type 2 diabetes.11 Rosiglitazone (branded as Avandia) is a PPAR-gamma-agonist drug that increases insulin sensitivity in fat cells. It has been withdrawn from foreign markets due to an increase in cardiovascular events. When stem cells in white fat are exposed to this during a critical stage of development, they turn into beige cells that can be activated by a non-specific beta-agonist drug called isoproterenol to burn calories at a much faster rate. Part of this effect was due to an increase in UCP1 and PGC1-alpha, both of which were mentioned earlier.
Brown and beige fat are the focus of intense pharmaceutical research, and hold great potential as part of the arsenal against obesity or unwanted weight gain. There are numerous behavioral techniques that can increase the contribution of brown and beige fat in total energy expenditure (calorie burning), but they require discipline and some tolerance to discomfort. Supplements are also available that act on brown and beige fat.
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2. van Marken Lichtenbelt WD, Vanhommerig JW, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med 2009;360:1500-8.
3. Vijgen GH, Bouvy ND, et al. Brown adipose tissue in morbidly obese subjects. PLoS One 2011;6:e17247(6 pp).
4. Lichtenbelt Wv, Kingma B, et al. Cold exposure – an approach to increasing energy expenditure in humans. Trends Endocrinol Metab 2014;25:165-7.
5. Gospodarska E, Nowialis P, et al. Mitochondrial turnover: A phenotype distinguishing brown adipocytes from interscapular brown adipose tissue and white adipose tissue. J Biol Chem February 1, 2015. [Epub, ahead of print]
6. Irving BA, Still CD, et al. Does IRISIN Have a BRITE Future as a Therapeutic Agent in Humans? Curr Obes Rep 2014;3:235-241.
7. Ockenga J, Valentini L, et al. Plasma bile acids are associated with energy expenditure and thyroid function in humans. J Clin Endocrinol Metab 2012;97:535-42.
8. Zhang Z, Zhang H, et al. Berberine activates thermogenesis in white and brown adipose tissue. Nat Commun 2014 Nov 25;5:5493(15 pp).
9. Mullur R, Liu YY, et al. Thyroid hormone regulation of metabolism. Physiol Rev 2014;94:355-82.
10. Cypess AM, Weiner LS, et al. Activation of Human Brown Adipose Tissue by a β3-Adrenergic Receptor Agonist. Cell Metab 2015;21:33-8.
11. Bartesaghi S, Hallen S, et al. Thermogenic Activity of UCP1 in Human White Fat-Derived Beige Adipocytes. Mol Endocrinol 2015;29:130-9.
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