NEW STUDY:

By Steve Blechman

The body has two forms of fat: white fat (bad fat) and brown fat (good fat). Brown fat burns calories. The capability of harnessing one’s own brown fat 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 this are being explored at major research centers and universities worldwide, with great excitement. Brown fat research is a hot topic today! Research has shown the more brown fat you have, the less likely you are of developing obesity and diabetes.

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 MEDITERANEAN 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.

References:

1. 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 

2. 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. www.sciencedaily.com/releases/2019/08/190821135238.htm 

3. 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 

4. 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 

5. 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.

6. 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. 

7. 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

8. 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. https://doi.org/10.1155/2014/239750. 

9. 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.

10. Yoon M-S. The emerging role of branched-chain amino acids in insulin resistance and metabolism. Forum Nutr, 2016; 8: 405-17.

11. Binder E, Bermudez-Silva FJ, Andre C et al. Leucine supplementation protects from insulin resistance by regulating adiposity levels. PLoS One, 2013; 8:e74705. 

12. 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.

13. Lynch, C.J. and Adams, SH (2014) Branched-chain amino acids in metabolic signaling and insulin resistance. Nat Rev Endrocrinol 10, 723-736.

14. 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.

15. 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

16. 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. https://doi.org/10.1371/journal.pmed.1002179

17. 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

18. 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 https://doi.org/10.2337/db16-1475 

19. 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. 

20. 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. https://doi.org/10.1155/2018/4207067.

21. 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.

22. 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

23. 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, https://doi.org/10.3945/ajcn.116.140640. 

24. 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. http://doi.org/10.1152/ajpendo.00198.2012

25. 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. https://doi.org/10.1371/journal.pone.0074705

26. 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. 

27. 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.

28. 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

29. THE THERMO HEAT® LOW-CARB MEDITERRANEAN DIET: WHY IT’S THE HEALTHIEST & BEST DIET FOR 2019 by Steve Blechman, https://advancedmolecularlabs.com/blogs/news/the-thermo-heat%C2%AE-low-carb-mediterranean-diet-why-it-s-the-healthiest-best-diet-for-2019

30. US News & World Report; Jan 2nd, 2019 What's the Best Diet for 2019? Experts Weigh In by By Serena Gordon https://www.usnews.com/news/health-news/articles/2019-01-02/whats-the-best-diet-for-2019-experts-weigh-in

31. 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.