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How to Activate Brown Fat to Lose Weight: From Natural Approaches to Pharmaceutical Insights

Over 70 percent of Americans are overweight. The Centers for Disease Control and Prevention (CDC) said that just being overweight, not obese, can result in severe illness and even premature death!

In 2022, many new studies have been published in the scientific literature supporting the potential weight loss/fat loss and health benefits of brown fat. And for the past 5 years, I have written many articles on the health and fat-loss benefits of brown adipose tissue (brown fat).

Join us on a journey through the nuances of brown fat's activity, its influence on metabolism, and the potential it holds to transform the landscape of weight loss strategies.

What is Brown Fat?

Brown fat (adipose) is a metabolically active tissue that dissipates energy as heat rather than storing it as fat. It helps humans acclimatize to cold, and may be critical for weight maintenance.

The widely held belief that all body fat is bad is currently being heavily scrutinized, due to the recent discovery of a different type of fat in humans known as brown fat. This type of body fat can actually burn off energy in the form of heat by a process known as thermogenesis, which can ultimately reduce overall body fat.

The body has two forms of fat: white fat, or unwanted fat that can lie directly underneath the skin, and brown fat, which often is found in the shoulder blade region or the neck. Unlike white fat, brown fat is good fat as it can help burn more calories. The more brown fat you have, the more calories you burn.

Brown fat is packed with mitochondria loaded with UCP-1, the protein that uncouples fat burning with ATP (energy) production instead of converting the energy into heat via thermogenesis, making the mitochondria effectively the furnace of the cell. The emergence of brown fat as a readily available fat-burning furnace is revolutionary, but like any fire, it requires the proper kindling materials. The ability to get lean by producing extra brown fat, or enhancing the activity of existing brown fat, represents a promising way to burn fat and lose weight.

Several landmark discoveries and approaches to enhancing brown fat function are being explored at major research centers and universities worldwide, with great excitement. Brown fat research is a hot topic today.

Brown Fat Vs. White Fat

The body has two forms of fat – WHITE FAT and BROWN FAT. Brown fat burns calories. The more brown fat you have, the more calories you burn. The capability of harnessing one’s own brown fat for fat burning is revolutionary! The ability to get lean by producing extra brown fat and enhancing and activating existing brown fat represents a promising way to burn fat. Several landmark discoveries and approaches to the this are being explored at major research centers and universities worldwide with great excitement.

Understanding Brown Fat and Its Role in Weight Management

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 with Less 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?

I’ve mentioned that 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.

Can We Harness Brown Fat To Fight Obesity?

Individual differences in brown fat may play an important role in human obesity. Increasing brown fat production and activity might help people lose weight and control body fat (white adipose tissue). A study from the Dana-Farber Cancer Institute and the Department of Cell Biology at Harvard Medical School showed that a chemical regulator (PRDM16) controls brown fat production. Key nutrients influence PRDM16 activity. Supplementing them in the diet is an exciting new strategy for fighting fat and obesity. Cold exposure increases brown fat levels, but few people are willing to spend much time in a freezer. Nutritional supplements are a novel way of boosting brown fat activity and promoting fat loss. Supplementing with Advanced Molecular Labs (AML) Thermo Heat is an effective way of activating BAT without overly stimulating the sympathetic nervous system (fight-or-flight system).

Brown Fat Controls Energy Balance

Brown fat (brown adipose tissue, BAT) is a calorie-burning tissue in the human body that converts food energy directly into heat. BAT increases metabolic rate following overeating, thus preventing weight gain. Energy metabolism works through a series of coupled reactions. This means that energy released by breaking down fats, carbohydrates and proteins are captured in other reactions, such as making ATP (a high energy chemical) or storing fats and carbohydrates. Uncoupling occurs when the energy from food breakdown is released as heat instead of capturing it as ATP. Brown fat converts food energy directly into heat. Drug and supplement makers such as Advanced Molecular Labs (AML) Thermo Heat are targeting uncoupling in brown fat and other cells to increase metabolic rate, which will help people control body fat.

Harnessing Brown Fat To Burn More Calories

Brown fat is a highly thermogenic tissue that converts energy to heat instead of storing it as fat. A study from the Scripps Research Institute in La Jolla, California showed that the release of chemicals called PGC1-alpha and GADD45- gamma activate brown fat to turn up the metabolic furnace. These newly discovered chemicals show how brown fat could promote fat loss. The scientists injected the hormone into mice fat cells, which increased their energy expenditure. Other studies found that exercise increases PGC1-alpha levels and activates brown fat metabolism, which helps explain why intense exercise promotes fat loss, even though carbohydrates are the principal fuels during exercise at intensities above 65 percent of maximum effort. Heavy exercise causes more PGC1 production than moderate-intensity exercise.

Increase Brown Fat Naturally

Research has found that exposure to cold temperature (65 degrees Fahrenheit) and consumption of spicy foods such as capsaicin and capsinoids found in chili peppers can activate brown fat. Also the spices Grains of Paradise, ginger and cinnamon. Plus, research has found that caffeine and coffee can also increase brown fat, as well virgin olive oil and polyphenols found in grapes, grape skins and other fruits.

Brown fat accounts for as much as 10 percent of the fat mass in people living in cold climates, such as northern Finland. Individual differences in BAT content and activity play an important role in human obesity. Brown fat (adipose) is a metabolically active tissue that dissipates energy as heat rather than storing it as fat. It helps humans acclimatized to cold, and may be critical for weight maintenance. Researchers from the National Institutes of Health, led by Francesco Celi and Paul Lee, found a novel way of turning on brown fat and increasing caloric expenditure: sleep in a cooler room. Five men slept in one-month blocks at room temperatures varying between 66 and 81 degrees. Sleeping in the cold room doubled brown fat activity and improved insulin sensitivity and blood sugar regulation. Sleeping in a slightly cooler room might be an effective way to increase metabolism and promote weight loss.

Supplements, Pharmaceuticals, and Brown Fat

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.

Most recently a new study was published in New England Journal of Medicine (NEJM)and in the August issue of Cell Metabolism, reported by today’s (August 8. 2017) New York Times shows the level of circulating follicle-stimulating hormone (FSH) increases in menopausal women. A recent study shows that FSH binds to its receptor on white adipocytes (white fat cells) and results in a relatively low resting energy expenditure and increased adiposity (body fat.)

So, what does this mean? By blocking the FSH hormone, it can boost metabolism, reduce abdominal fat and slow bone loss. Most importantly it helps in the conversion of white fat into beige/brown fat. The more brown fat that we have, the more calories we will burn, and the more weight we will lose!

 Recently, the three most updated reviews on brown fat in 2017 and published in Obesity Reviews (August 2017 (first published online May 25, 2017) July 14, 2017, and February 10, 2017) show the positive effect of converting white fat to beige/brown fat and enhancing thermogenesis through pharmacological and nutritional modalities. Factors involved in the conversion of white to beige/brown fat can include certain drugs, but a safer approach can be nutrition, exercise, certain dietary supplements and spices such as capsaicin, the hot spice found in chili peppers.

The NEJM showed that abdominal fat was reduced significantly, but we already know that cold induced thermogenesis can enhance conversion of white fat into brown fat. Of course, cold is not a practical approach and it may not be pleasant, but if you have a high tolerance for cold: keep the air conditioning at high levels in the summer, wear as little clothing as possible and take cold showers!!  You may also want to try swimming in a cold pool, the ocean or live a brown-fat activating lifestyle and become a fat-burning machine!

For more authoritative information on brown fat see ThermoHeat Weight Loss Revolution, by Michael J. Rudolph, Ph.D, including the foreword by Daniel L. Friedman, MD and Eugene B Friedman, MD. You can click the link to order or order on Amazon here   The Thermo Heat Weight Loss Revolution is a groundbreaking scientific plan based on research involving brown fat (BAT.) The ThermoHeat Weight Loss Revolution offers its readers a brown fat, thermogenic and brown-fat-activating-diet supplements. You can also get a free PDF version here

Additionally, a section of this book is devoted to appropriate brown-fat activating exercise programs and food choices plus, an easy-to-follow thirty-day thermogenic, fat-burning meal plan. Followers of this scientifically developed program will find that they are able to harness the power of brown fat, maximize their energy. expenditure, attain, and then, maintain their ideal weight, and achieve the reduction of body fat and preservation of lean muscle they are looking for.

BCAA’s and Brown Fat

It was most recently reported in ScienceDaily (August 21, 2019), “Scientists have discovered how brown fat, also known as brown adipose tissue, may help protect against obesity and diabetes. Their study adds to our knowledge about the role of brown fat in human health and could lead to new medications for treating obesity and type 2 diabetes.” The study published in the prestigious journal Nature (August 21, 2019) found according to ScienceDaily, “brown fat could also help the body filter and remove branched-chain amino acids (BCAAs) from the blood.”

The article in ScienceDaily further explains, “In normal concentrations in the blood, these amino acids are essential for good health. In excessive amounts, they're linked to diabetes and obesity. The researchers found that people with little or no brown fat have reduced ability to clear BCAAs from their blood, and that may lead to the development of obesity and diabetes.”

The researchers continued, “The study also solved a 20-plus year mystery about brown fat: how BCAAs enter the mitochondria that generate energy and heat in cells. The scientists discovered that a novel protein (called SLC25A44) controls the rate at which brown fat clears the amino acids from the blood and uses them to produce energy and heat.”

“Our study explains the paradox that BCAA supplements can potentially benefit those with active brown fat, such as healthy people, but can be detrimental to others, including the elderly, obese and people with diabetes," said co-author Labros S. Sidossis, a Distinguished Professor who chairs the Department of Kinesiology and Health in the School of Arts and Sciences at Rutgers University-New Brunswick. He is also a professor in the Department of Medicine at Rutgers Robert Wood Johnson Medical School in Rutgers Biomedical and Health Sciences.

“Researchers next need to determine whether uptake of BCAAs by brown fat can be controlled by environmental factors -- such as exposure to mildly cold temperatures (65 degrees Fahrenheit) or consumption of spicy foods -- or by drugs. This could improve blood sugar levels that are linked to diabetes and obesity,” Sidossis said.

Research has shown the more brown fat you have, the more calories you burn. Also, the more brown fat you have, the less likely you are of becoming obese and developing obesity.

The Nature study says, “Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans.”

Branched-chain amino acids supplements (BCAAs) have been associated with insulin resistance in obese individuals. Recently, the valine catabolite 3-hydroxyisobutyrate (3-HIB) was shown to promote insulin resistance in skeletal muscle by increasing lipid content in vivo. The purpose of this study was to investigate the mechanistic effects of 3-HIB on skeletal muscle insulin signaling, metabolism, and related gene expression in vitro. These findings were recently published in the Journal of Nutrition Research (June 2019). This most recent study found that 3-HIB can reduce muscle insulin sensitivity and support a role of 3-HIB in the development of insulin resistance. This study is significant because it confirms the mechanism of 3-HIB and insulin resistance in muscle!

More recent studies have confirmed that the branched-chain amino acid valine metabolite 3-HIB is involved in the pathogenesis of insulin resistance in skeletal muscle and might be involved in insulin resistance in humans (Diabetes, July 2017; EbioMedicine, 2018; J Diab Rsch, 2018). Unlike valine, leucine has been shown to improve insulin function. Leucine consumption alone has been shown to rescue insulin-signaling deficiency (PLoS, 2011). Research has shown that leucine enhances the effects of the diabetic drug metformin on insulin sensitivity and glycemic control (Metabolism, November 2016; July 2015). A most recent study (Exp Clin Endocrinol Diabetes, 2018) found that oral administration of leucine improved endothelial function in healthy individuals when infused with glucose. Acute hyperglycemia impairs endothelial function in healthy individuals. This study found that leucine administration prevented hyperglycemia-mediated endothelial function. 

Unlike leucine, which avoids insulin resistance by increasing mitochondrial-driven fat loss, valine does not encourage mitochondrial biogenesis. Impaired mitochondrial function in skeletal muscle is one of the major predisposing factors to metabolic diseases, such as insulin resistance, type 2 diabetes and cardiovascular disease. Leucine supplementation increases brown fat thermogenesis, energy expenditure and insulin sensitivity by activating SIRT1 activity. SIRT1 is known to “promote mitochondrial biogenesis and oxidative capacity and prevent the mitochondrial dysfunction in skeletal muscle” (Journal of Nutrition and Metabolism, 2014). Leucine may also attenuate adiposity and promote weight loss during energy restriction (Nutrition 2006, Diabetes, 2007). These effects are in part by activating the SIRT1-dependent pathway, stimulating mitochondrial biogenesis, brown fat thermogenesis and oxygen consumption (Nutrition Metabolism, 2008). Mitochondrial biogenesis and SIRT1 expression in skeletal muscle has also been shown to increase life span in middle-aged mice (Cell Metabolism, 2010). As far as isoleucine is concerned, unlike valine, it has been shown to improve insulin sensitivity by increasing glucose into muscle cells (Am J Physiol Endocrinol Metab, 2007).

It’s clear based on scientific research that the high-circulating BCAA valine is associated with obesity and diabetes. The latest available literature has shown that the branched-chain amino acid valine (catabolite 3-HIB) is most likely the probable cause of insulin resistance!

The book entitled Thermo Heat® Weight Loss Revolution by Michael Rudolph, Ph.D. outlines, in chapter 2, The Thermo Heat HIIT Workout, plus The Thermo Heat Total-Body Fat-Incinerating Exercise Plan. It says that you should limit yourself to 100 grams of carbohydrates per day, or less. Additionally, a section of this book is devoted to appropriate brown fat-activating exercise programs and food choices, plus an easy-to-follow 30-day thermogenic, fat-burning meal plan. Followers of this scientifically developed program will find that they are able to harness the power of brown fat, maximize their energy expenditure, attain and then maintain their ideal weight, and achieve the reduction of body fat and preservation of lean muscle they are looking for.

Over the last few years, I launched AML® THERMO HEAT, the most scientifically advanced brown fat and thermogenic supplement line ever developed (see the AML® Thermo Heat™ Ultimate Fat Burning Stack!) One of those products, AML™ THERMO HEAT® FAT BURNING PROTEIN, contains nutrients that have been shown to increase brown fat activation and thermogenesis, including 5 grams of the amino acid leucine. Also, nitric oxide has been shown to activate BAT and thermogenesis. Nitric oxide and nitric oxide precursors such as citrulline have been shown to increase BAT and thermogenesis. Grapeskin extract has been shown to increase nitric oxide production. Polyphenols are being studied for their role in fat metabolism and obesity management. Folic acid also boosts nitric oxide availability, by increasing BH4 and decreasing homocysteine levels. 

Research has shown that folic acid can lower homocysteine levels, increase insulin sensitivity and lower fasting insulin levels in type 2 diabetes. Medium-chain triglycerides (MCTs), grains of paradise (40mg - standardized for 12% paradol, a clinically effective dose) and BioPerine® black pepper fruit extract are all included for further activation of brown adipose tissue (BAT) and thermogenesis. Grains of paradise, a spice containing 6-paradol, like chili peppers containing capsaicin, activate BAT, increase whole-body energy expenditure and decrease visceral fat (deep abdominal fat) in humans. Allulose is added as a natural, low-calorie, fat burning, thermogenic sweetener. It is approved for low-sugar/low-carb or ketogenic diets. Allulose does not impact blood sugar or insulin levels.

Don’t think you can lose weight and enhance fat loss by taking just one fat-burning pill a day! That’s why I developed the AML®THERMO HEAT ADVANCED DIET, NUTRITION, SUPPLEMENTATION AND EXERCISE PROGRAM for maximizing brown fat, brown fat activity and 24-hour energy expenditure! Check out the AML ®THERMO HEAT LOW-CARB MEDITERRANEAN DIET and why I feel it’s the best overall diet for weight loss, fat loss and optimal health! It’s rich in healthy fats and not bad fats that activate brown fat thermogenesis (see my other article on good fats and bad fats.)

Like I said earlier, the ability to burn fat by producing extra brown fat and enhancing existing brown fat for fat burning is revolutionary! The most recent Nature breakthrough study on brown fat is informative and promising in the ongoing battle against obesity and diabetes. As more research develops about brown fat, the future looks compelling in conquering the obesity war by following a brown fat-activating lifestyle.

Additional Benefits of Brown Fat

It was also reported in ScienceDaily on January 4, 2021 that “A new study in Nature offers strong evidence: among over 52,000 participants, those who had detectable brown fat were less likely than their peers to suffer cardiac and metabolic conditions ranging from type 2 diabetes to coronary artery disease, which is the leading cause of death in the United States.

The Nature report acknowledged that individuals with more brown fat had lower risk of type 2 diabetes, elevated blood lipids, cardiovascular disease, cerebral vascular disease, congestive heart failure and hypertension.

“The study, by far the largest of its kind in humans, confirms and expands the health benefits of brown fat suggested by previous studies. For the first time, it reveals a link to lower risk of certain conditions,” says Paul Cohen, the Albert Resnick, M.D., Assistant Professor and senior attending physician at The Rockefeller University Hospital. “These findings make us more confident about the potential of targeting brown fat for therapeutic benefit.”


In the realm of weight management and metabolic health, the enigmatic world of brown fat holds both mystery and promise. As we traverse the intricacies of its activation and potential, it becomes evident that this unique tissue is more than just a scientific curiosity—it's a potential game-changer in the battle against obesity. From the natural strategies that harness the power of cold exposure and dietary choices, to the pharmaceutical breakthroughs that could reshape obesity treatment, brown fat stands as a beacon of hope.

With every revelation, we inch closer to deciphering the language of brown fat, unraveling its secrets, and uncovering novel pathways for healthier living. As researchers tirelessly explore its nuances and individuals incorporate brown fat-activating practices into their lifestyles, we find ourselves at the cusp of a transformative era. The journey to understanding brown fat is far from over; it's a road paved with discovery, innovation, and the promise of a healthier, more vibrant future.

In embracing the potential of brown fat, we embrace a future where the body's own mechanisms hold the key to unlocking vitality and well-being. Let this journey be a reminder that within the complexities of biology, there lies a source of power—one that might just redefine how we approach weight management, ignite metabolism, and propel us toward a healthier, happier tomorrow.



  1. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004;84:277-359.
  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.
  12. (Diabetes, Published Online June 22, 2014)
  13. (Proceedings National Academy of Sciences, doi: 10.1073
  14. (Current Opinion Clinical Nutritional Metabolic Care, 17:368-372, 2014)
  15. (Scientific American, August 2014)
  16. Takeshi Yoneshiro et al. BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. Nature, August 21, 2019 DOI: 10.1038/s41586-019-1503-x 
  17. Rutgers University. Why brown fat is good for people's health: Study may help lead to drugs aimed at diabetes and obesity. ScienceDaily, 21 August 2019. 
  18. Lyon, Emily S; Rivera, Madison E; Johnson, Michele A; Sunderland, Kyle L; Vaughan, Roger A. Actions of chronic physiological 3-hydroxyisobuterate treatment on mitochondrial metabolism and insulin signaling in myotubes. Nutrition Research, June 2019. Vol: 66, Page: 22. DOI 10.1016/j.nutres.2019.03.012 
  19. Cummings, NE, Williams, EM, Kasza, I, Konon, et al. (2018), Restoration of metabolic health by decreased consumption of branched‐chain amino acids. J Physiol, 596: 623-645. doi:10.1113/JP275075 
  20. Zheng Y, Li Y, Qi Q et al. Cumulative consumption of branched-chain amino acids and incidence of type 2 diabetes. Int J Epidemiol, 2016; 45: 1482-92.
  21. Isanejad M, LaCroix AZ, Thomson CA et al. Branched-chain amino acid, meat intake and risk of type 2 diabetes in the Women’s Health Initiative. Br J Nutr, 2017; 117:1523-30. 
  22. Newgard CB, An J, Bain JR et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab, 2009; 9: 311-26
  23. Chunzi Liang, Benjamin J Curry, Patricia L Brown, and Michael B Zemel. Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes. Journal of Nutrition and Metabolism, vol. 2014, Article ID 239750, 11 pages, 2014.
  24. Lee CC, Watkins SM, Lorenzo C et al. Branched-chain amino acids and insulin metabolism: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care, 2016; 39: 582-8.
  25. Yoon M-S. The emerging role of branched-chain amino acids in insulin resistance and metabolism. Forum Nutr, 2016; 8: 405-17.
  26. Binder E, Bermudez-Silva FJ, Andre C et al. Leucine supplementation protects from insulin resistance by regulating adiposity levels. PLoS One, 2013; 8:e74705. 
  27. Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes, 2007; 56: 1647-54.
  28. Lynch, C.J. and Adams, SH (2014) Branched-chain amino acids in metabolic signaling and insulin resistance. Nat Rev Endrocrinol 10, 723-736.
  29. Xiao, F, Yu, J, Guo, Y, Deng, J, Li, K, et al (2014) Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice. Metabolism 63, 841-850.
  30. Jang C, Oh, SF, et al A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat Med 22, 421-426
  31. Lotta LA, Scott RA, Sharp SJ, Burgess S, Luan J, et al. (2016) Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis. PLOS Medicine 13(11): e1002179.
  32. Avogaro, A and Bier, DM (1989.) Contribution of 3-hydroxyisobutyrate to the measurement of 3-hydroxybutyrate in human plasma: comparison of enzymatic and gas-liquid chromatography-mass spectrometry assays in normal and in diabetic subjects. J Lipid Res 30, 1811-1817
  33. Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion–Induced Insulin Resistance Lydia-Ann LS Harris, Gordon I Smith, Bruce W Patterson, Raja S Ramaswamy et al. Diabetes 2017;66:1871-1878
  34. Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes Mardinoglu, Adil et al. EBioMedicine, Volume 27, 151-155, Jan. 2018. 
  35. Ulrika Andersson-Hall, Carolina Gustavsson, Anders Pedersen, Daniel Malmodin, Louise Joelsson, and Agneta Holmäng. Higher Concentrations of BCAAs and 3-HIB Are Associated with Insulin Resistance in the Transition from Gestational Diabetes to Type 2 Diabetes. Journal of Diabetes Research, vol. 2018, Article ID 4207067, 12 pages, 2018.
  36. Macotela, Y Emanuelli, B, Bang, AM et al. (2011) Dietary leucine – an environmental modifier of insulin resistance acting on multiple levels of metabolism. PLoS One 6, e21187.
  37. Increasing Dietary Leucine Intake Reduces Diet-Induced Obesity and Improves Glucose and Cholesterol Metabolism in Mice via Multimechanisms. Y. Zhang, K. Guo, R.E. LeBlanc, D. Loh, G.J. Schwartz, Y. Yu Diabetes Jun 2007, 56 (6) 1647-1654; DOI: 10.2337/db07-0123
  38. Sina S Ullrich, Penelope CE Fitzgerald, Gudrun Schober, Robert E Steinert, Michael Horowitz, Christine Feinle-Bisset; Intragastric administration of leucine or isoleucine lowers the blood glucose response to a mixed-nutrient drink by different mechanisms in healthy, lean volunteers, The American Journal of Clinical Nutrition, Volume 104, Issue 5, 1 November 2016, Pages 1274-1284,
  39. Li, H, Xu, M, Lee, J, He, C, & Xie, Z (2012). Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice. American Journal of Physiology - Endocrinology and Metabolism, 303(10), E1234-E1244.
  40. Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels. Binder E, Bermúdez-Silva FJ, André C, Elie M, Romero-Zerbo SY, et al. (2013) Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels. PLOS ONE 8(9): e74705.
  41. Activation of the AMPK/Sirt1 pathway by a leucine-metformin combination increases insulin sensitivity in skeletal muscle, and stimulates glucose and lipid metabolism and increases life span in Caenorhabditis elegans. Banerjee, Jheelam et al. Metabolism – Clinical and Experimental, Volume 65, Issue 11, 1679-1691. November 2016. 
  42. The Thermo Heat® Weight Loss Revolution, by Michael J. Rudolph, Ph.D, including the foreword by Daniel L. Friedman, MD and Eugene B Friedman, MD.
  43. Cara B Ebbeling, Henry A Feldman, Gloria L Klein, Julia M W Wong, Lisa Bielak, Sarah K Steltz, Patricia K Luoto, Robert R Wolfe, William W Wong, David S Ludwig. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. BMJ, 2018; k4583 DOI: 10.1136/bmj.k4583
  45. US News & World Report; Jan 2nd, 2019 What's the Best Diet for 2019? Experts Weigh In by By Serena Gordon
  46. Leucine amplifies the effects of metformin on insulin sensitivity and glycemic control in diet-induced obese mice. Fu, Lizhi et al. Metabolism - Clinical and Experimental, Volume 64, Issue 7, 845-856. July 2015.
  47. Giving brown fat a boost to fight type 2 diabetes. UT Southwestern Medical Center. June 4, 2021. Medical Xpress
  48. Gallardo-Montejano, V.I., Yang, C., Hahner, L. et al. Perilipin 5 links mitochondrial uncoupled respiration in brown fat to healthy white fat remodeling and systemic glucose tolerance. Nat Commun 12, 3320, June 3, 2021.
  49. Van Schaik L, Kettle C, Green R, Irving HR, Rathner JA. Effects of Caffeine on Brown Adipose Tissue Thermogenesis and Metabolic Homeostasis: A Review. Front Neurosci. 2021 Feb 4;15:621356. doi: 10.3389/fnins.2021.621356. PMID: 33613184; PMCID: PMC7889509.
  50. Duarte L, Gasaly N, Poblete-Aro C, Uribe D, Echeverria F, Gotteland M, Garcia-Diaz DF. Polyphenols and their anti-obesity role mediated by the gut microbiota: a comprehensive review. Rev Endocr Metab Disord. 2021 Jun;22(2):367-388. doi: 10.1007/s11154-020-09622-0. Epub 2021 Jan 2. PMID: 33387285.
  51. Yoneshiro T, Matsushita M, Sugita J, Aita S, Kameya T, Sugie H, Saito M. Prolonged Treatment with Grains of Paradise (Aframomum melegueta) Extract Recruits Adaptive Thermogenesis and Reduces Body Fat in Humans with Low Brown Fat Activity. J Nutr Sci Vitaminol (Tokyo). 2021;67(2):99-104. doi: 10.3177/jnsv.67.99. PMID: 33952741.
  52. Monfort-Pires M, U-Din M, Nogueira GA, de Almeida-Faria J, Sidarta-Oliveira D, Sant'Ana MR, De Lima-Júnior JC, Cintra DE, de Souza HP, Ferreira SRG, Sapienza MT, Virtanen KA, Velloso LA. Short Dietary Intervention with Olive Oil Increases Brown Adipose Tissue Activity in Lean but not Overweight Subjects. J Clin Endocrinol Metab. 2021 Jan 23;106(2):472-484. doi: 10.1210/clinem/dgaa824. PMID: 33180910.
  53. Álvarez-Artime A, García-Soler B, Sainz RM, Mayo JC. Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour. Int J Mol Sci. 2021 May 24;22(11):5560. doi: 10.3390/ijms22115560. PMID: 34074045.
  54. Cheng L, Wang J, Dai H, Duan Y, An Y, Shi L, Lv Y, Li H, Wang C, Ma Q, Li Y, Li P, Du H, Zhao B. Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus. Adipocyte. 2021 Dec;10(1):48-65. doi: 10.1080/21623945.2020.1870060. PMID: 33403891; PMCID: PMC7801117.
  55. Becher T, Palanisamy S, Kramer DJ, Eljalby M, Marx SJ, Wibmer AG, Butler SD, Jiang CS, Vaughan R, Schöder H, Mark A, Cohen P. Brown adipose tissue is associated with cardiometabolic health. Nat Med. 2021 Jan;27(1):58-65. doi: 10.1038/s41591-020-1126-7. Epub 2021 Jan 4. PMID: 33398160.
  56. Suchacki, Karla J.; Stimson, Roland H. 2021. "Nutritional Regulation of Human Brown Adipose Tissue" Nutrients 13, no. 6: 1748.
  57. Irandoost P, Lotfi Yagin N, Namazi N, Keshtkar A, Farsi F, Mesri Alamdari N, Vafa M. The effect of Capsaicinoids or Capsinoids in red pepper on thermogenesis in healthy adults: A systematic review and meta-analysis. Phytother Res. 2021 Mar;35(3):1358-1377. doi: 10.1002/ptr.6897. Epub 2020 Oct 15. PMID: 33063385.
  58. An update on brown adipose tissue biology: a discussion of recent findings. Rafael C. Gaspar, José R. Pauli, Gerald I. Shulman, and Vitor R. Muñoz. American Journal of Physiology-Endocrinology and Metabolism 2021 320:3, E488-E495
  59. Li X, Lu HY, Jiang XW, Yang Y, Xing B, Yao D, Wu Q, Xu ZH, Zhao QC. Cinnamomum cassia extract promotes thermogenesis during exposure to cold via activation of brown adipose tissue. J Ethnopharmacol. 2021 Feb 10;266:113413. doi: 10.1016/j.jep.2020.113413. Epub 2020 Sep 24. PMID: 32980484.
  60. Choi Y, Yu L. Natural Bioactive Compounds as Potential Browning Agents in White Adipose Tissue. Pharm Res. 2021 Apr;38(4):549-567. doi: 10.1007/s11095-021-03027-7. Epub 2021 Mar 30. PMID: 33783666; PMCID: PMC8082541.
  61. Shams, Ramsha; Drasites, Kelsey P.; Zaman, Vandana; Matzelle, Denise; Shields, Donald C.; Garner, Dena P.; Sole, Christopher J.; Haque, Azizul; Banik, Narendra L. 2021. The Pathophysiology of Osteoporosis after Spinal Cord Injury, Int. J. Mol. Sci. 22, no. 6: 3057.
  62. Maliszewska K, Kretowski A. Brown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis. Int J Mol Sci. 2021;22(4):1530. Published 2021 Feb 3. doi:10.3390/ijms22041530
  63. Payab M, Abedi M, Foroughi Heravani N, Hadavandkhani M, Arabi M, Tayanloo-Beik A, Sheikh Hosseini M, Gerami H, Khatami F, Larijani B, Abdollahi M, Arjmand B. Brown adipose tissue transplantation as a novel alternative to obesity treatment: a systematic review. Int J Obes (Lond). 2021 Jan;45(1):109-121. doi: 10.1038/s41366-020-0616-5. Epub 2020 Jun 4. PMID: 32499525.
  64. Goubern M, Yazbeck J, Senault C, Portet R. Non-shivering thermogenesis and brown adipose tissue activity in essential fatty acid deficient rats. Arch Int Physiol Biochim. 1990 Aug;98(4):193-9. doi: 10.3109/13813459009113977. PMID: 1707615.
  65. Bazyar H, Zare Javid A, Bavi Behbahani H, Moradi F, Moradi Poode B, Amiri P. Consumption of melatonin supplement improves cardiovascular disease risk factors and anthropometric indices in type 2 diabetes mellitus patients: a double-blind, randomized, placebo-controlled trial. Trials. 2021 Mar 25;22(1):231. doi: 10.1186/s13063-021-05174-z. PMID: 33766084; PMCID: PMC7995760.
  66. Genario R, Cipolla-Neto J, Bueno AA, Santos HO. Melatonin supplementation in the management of obesity and obesity-associated disorders: A review of physiological mechanisms and clinical applications. Pharmacol Res. 2021 Jan;163:105254. doi: 10.1016/j.phrs.2020.105254. Epub 2020 Oct 17. PMID: 33080320.
  67. Sentis SC, Oelkrug R, Mittag J. Thyroid hormones in the regulation of brown adipose tissue thermogenesis. Endocr Connect. 2021 Feb;10(2):R106-R115. doi: 10.1530/EC-20-0562. PMID: 33491659; PMCID: PMC7983518.
  68. Ecole Polytechnique Fédérale de Lausanne. Bile acids trigger satiety in the brain. ScienceDaily, 24 May 2021.
  69. Nascimento EBM, Moonen MPB, Remie CME, Gariani K, Jörgensen JA, Schaart G, Hoeks J, Auwerx J, van Marken Lichtenbelt WD, Schrauwen P. Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans. J Clin Endocrinol Metab. 2021 Apr 23;106(5):1437-1447. doi: 10.1210/clinem/dgaa960. PMID: 33524145.
  70. Rockefeller University. Study of 50,000 people finds brown fat may protect against numerous chronic diseases. ScienceDaily, 4 January 2021.>.
  71. UT Southwestern Medical Center. Giving brown fat a boost to fight type 2 diabetes: Increasing a protein concentrated in brown adipose tissue remodels white adipose tissue to lower diabetes risk, study suggests. ScienceDaily, 4 June 2021.>.
  72. Fu P, Zhu R, Jia J, Hu Y, Wu C, Cieszczyk P, Holmberg HC, Gong L. Aerobic exercise promotes the functions of brown adipose tissue in obese mice via a mechanism involving COX2 in the VEGF signaling pathway. Nutr Metab (Lond). 2021 Jun 3;18(1):56. doi: 10.1186/s12986-021-00581-0. PMID: 34082784; PMCID: PMC8176720.
  73. Loeliger RC, Maushart CI, Gashi G, Senn JR, Felder M, Becker AS, Müller J, Balaz M, Wolfrum C, Burger IA, Betz MJ. Relation of diet-induced thermogenesis to brown adipose tissue activity in healthy men. Am J Physiol Endocrinol Metab. 2021 Jan 1;320(1):E93-E101. doi: 10.1152/ajpendo.00237.2020. Epub 2020 Nov 23. PMID: 33225717.
  74. Pinckard KM, Shettigar VK, Wright KR, Abay E, Baer LA, Vidal P, Dewal RS, Das D, Duarte-Sanmiguel S, Hernández-Saavedra D, Arts PJ, Lehnig AC, Bussberg V, Narain NR, Kiebish MA, Yi F, Sparks LM, Goodpaster BH, Smith SR, Pratley RE, Lewandowski ED, Raman SV, Wold LE, Gallego-Perez D, Coen PM, Ziolo MT, Stanford KI. A Novel Endocrine Role for the BAT-Released Lipokine 12,13-diHOME to Mediate Cardiac Function. Circulation. 2021 Jan 12;143(2):145-159. doi: 10.1161/CIRCULATIONAHA.120.049813. Epub 2020 Oct 27. PMID: 33106031; PMCID: PMC7856257.
  75. Santhanam P, Rowe SP, Solnes LB, Quainoo B, Ahima RS. A systematic review of imaging studies of human brown adipose tissue. Ann N Y Acad Sci. 2021 Feb 18. doi: 10.1111/nyas.14579. Epub ahead of print. PMID: 33604891.
  76. Gavaldà-Navarro A, Villarroya J, Cereijo R, Giralt M, Villarroya F. The endocrine role of brown adipose tissue: An update on actors and actions. Rev Endocr Metab Disord. 2021 Mar 12. doi: 10.1007/s11154-021-09640-6. Epub ahead of print. PMID: 33712997.
  77. Andrea Méndez, Concepción M Aguilera et al. Exercise-induced changes on exerkines that might influence brown adipose tissue metabolism in young sedentary adults. European Journal of Sport Science, February 2022. DOI:10.1080/17461391.2022.2040597
  78. J Zapata, A Gallardo et al. n-3 polyunsaturated fatty acids in the regulation of adipose tissue browning and thermogenesis in obesity: Potential relationship with gut microbiota. Prostaglandins, Leukotrienes and Essential Fatty Acids, February 2022. DOI:
  79. Ivan Luiz Padilha Bonfanteet al. Combined training increases thermogenic fat activity in patients with overweight and type 2 diabetes. Int J Obes (Lond), 2022.
  80. Claudia Pivonello, Mariarosaria Negri et al. The role of melatonin in the molecular mechanisms underlying metaflammation and infections in obesity: A narrative review. Obes Rev, 2022 Mar. DOI: 10.1111/obr.13390
  81. Jing Yu, Jiabing Zhuet al. Dopamine receptor D1 signaling stimulates lipolysis and browning of white adipocytes. Biophys Res Commun, 2022. DOI: 10.1016/j.bbrc.2021.12.040
  82. Jasleen Kaur, Vijay Kumaret al. Combination of TRP channel dietary agonists induces energy expending and glucose utilizing phenotype in HFD-fed mice. Int J Obes (Lond). 2022 Jan. DOI: 10.1038/s41366-021-00967-3
  83. Paul Trayhurn. Brown Adipose Tissue: A Short Historical Perspective. Methods Mol Biol, 2022. DOI: 10.1007/978-1-0716-2087-8_1
  84. Felix T Yang, Kristin I Stanford. Batokines: Mediators of Inter-Tissue Communication (a Mini-Review). Curr Obes Rep, 2022. DOI: 10.1007/s13679-021-00465-7
  85. Ana Paula Azevêdo Macêdoet al. 12,13-diHOME as a new therapeutic target for metabolic diseases. Life Sci, 2022. DOI: 10.1016/j.lfs.2021.120229
  86. Ming-Sheng Ye, Liping Luo et al. KCTD10 regulates brown adipose tissue thermogenesis and metabolic function via Notch signaling. J Endocrinol, 2022. DOI: 10.1530/JOE-21-0016
  87. Kirsi A Virtanen. In Vivo Imaging of Brown Adipose Tissue in Humans: FDG-PET/CT and Beyond. Methods Mol Biol, 2022. DOI: 10.1007/978-1-0716-2087-8_18
  88. Juro Sakai. [β-Adrenergic Signaling Regulates a Concerted Thermogenic Response in Brown Adipose Tissue and White Adipose Tissue]. Brain Nerve, 2022 Feb. DOI: 10.11477/mf.1416202000