Excess body weight is associated with many health concerns, and is rapidly becoming the number one health problem worldwide. among the health risks are diabetes, cardiovascular disease, cancer and premature death. (1) Individuals of the obese classification are especially subject to deleterious health implications. Obesity results in:
Visceral Fat - Obesity results in increases of visceral fat. Visceral fat (also known as belly fat) is the fat that accumulates around organs in the abdominal cavity and is linked to serious diseases, including type 2 diabetes. metabolic syndrome and those affecting organ functioning. Significant levels of inflammatory proteins are generated by visceral fat. In fact, inflammation of the liver which precedes HDLF, is mediated by visceral fat inflammatory proteins.(2)
Nonalcoholic fatty liver disease (NAFLD) - Obesity is a significant risk factor in the development of NAFLD. Most noteworthy, is the excessive buildup of triglycerides in the liver which causes metabolic disturbances throughout the body. As a result, fatty acid metabolism becomes impaired, which may lead to fatty acid intermediates which causes insulin resistance and cardiovascular disease.
Adipose Tissue and Aging - White adipose tissue, associated with obesity, is the most affected tissue in aging. As the adipose tissue ages, there is a significant increase in oxidative stress and the generation of inflammatory proteins resulting in chronic low grade inflammation. In turn, this further damages tissue and accelerates aging. (6)
HYPER LONGEVITY™ (Ursolic Acid | Rosmarinic Acid)
(1) Unamuno Xm et al. Adipokine dysregulation and adipose tissue inflammation in human obesity. Eur J Clin Invest. 2018 Sep
(2) Casagrande BP, et al. Hepatic inflammation precedes steatosis and is mediated by visceral fat accumulation. J Endocrinol. 2020 Mar 1
(3) Conceição G, et al. Fat Quality Matters: Distinct Proteomic Signatures Between Lean and Obese Cardiac Visceral Adipose Tissue Underlie its Differential Myocardial Impact. Cell Physiol Biochem. 2020 Apr 23
(4) Huang N, et al. Novel insight into perirenal adipose tissue: A neglected adipose depot linking cardiovascular and chronic kidney disease. World J Diabetes, 2020 Apr 15
(5) Sreedhar UL, et al. A Systematic Review of Intra-pancreatic Fat Deposition and Pancreatic Carcinogenesis. J Gastrointest Surg. 2019 Nov 20
(6) Yu Q, et al. Sample multiplexing for targeted pathway proteomics in aging mice. Proc Natl Acad Sci USA. 2020 Apr 24
(7) Mangge H, et al. Telomere shortening associates with elevated insulin and nuchal fat accumulation. Sci Rep. 2020 Apr 22
(8) Goldberg EL, et al. How Inflammation Blunts Innate Immunity in Aging. Interdiscip Top Gerontol Geiatr. 2020
(9) Conley SM, et al. Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells. Front Cell Dev Biol. 2020 Mar 26
(10) Eckel-Mahan K, et al. Adipose Stromal Cell Expansion and Exhaustion: Mechanisms and Consequences. Cells 2020 Apr 2
(11) Wang Y, et al. Berberine inhibits free fatty acid and LPS-induced inflammation via modulating ER stress response in macrophages and hepatocytes. PLoS One. 2020 May 1
(12) Horvath C, et al. Feeding brown fat: dietary phytochemicals targeting non-shivering thermogenesis to control body weight. Proc Nutr Soc, 2020 Apr
(13) Wang C, et al. Berberine inhibits adipocyte differentiation, proliferation and adiposity through down-regulating galectin-3.
(14) Yu SJ, et al. Berberine alleviates insulin resistance by reducing peripheral branched-chain amino acids. Am J Physiol Endocrinol Metab. 2019 Jan
(15) Su T, et al. Apigenin inhibits STAT3/CD36 signaling axis and reduces visceral obesity. Pharmacol Res. 2020 Feb
(16) Jung UJ, et al. Apigenin Ameliorates Dyslipidemia, Hepatic Steatosis and Insulin Resistance by Modulating Metabolic and Transcriptional Profiles in the Liver of High-Fat Diet-Induced Obese Mice. Nutrients. 2016 May
(16) Yaribeygi H, et al. Antidiabetic potential of saffron and its active constituents. J Cell Physiol, 2019 Jun
(17) Mashmoul M, et al. Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats. BMC Complement Altern Med. 2016 Oct
(18) Al-Saud NBS. Impact of curcumin treatment on diabetic albino rats. Saudi J Biol Sci. 2020 Feb;27
(19) Gaballah HH, et al, Mitigative effects of the bioactive flavonol fisetin on high-fat/high-sucrose induced nonalcoholic fatty liver disease in rats.
(20) Kim M, et al. Lemon Balm and Its Constituent, Rosmarinic Acid, Alleviate Liver Damage in an Animal Model of Nonalcoholic Steatohepatitis. Nutrients. 2020 Apr 22
(21) Rui Y, et al. Rosmarinic acid suppresses adipogenesis, lipolysis in 3T3-L1 adipocytes, lipopolysaccharide-stimulated tumor necrosis factor-α secretion in macrophages, and inflammatory mediators in 3T3-L1 adipocytes. Food Nutr Res. 2017 Jun
(22) Younossi ZM, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 2016 Jul;
(23) Milton-Laskibar L, et al. Effects of resveratrol and its derivative pterostilbene on brown adipose tissue thermogenic activation and on white adipose tissue browning process. J Physiol Biochem. 2020 Mar 13
(24) Gomez-Zorita S, et al. Effects of Pterostilbene on Diabetes, Liver Steatosis and Serum Lipids. Curr Med Chem. 2019 Oct 29
(25) Gonzales-Garibay AS, et al, Effect of Ursolic Acid on Insulin Resistance and Hyperinsulinemia in Rats with Diet-Induced Obesity: Role of Adipokines Expression. J Med Food. 2020 Mar;23
Energy generation from brown adipose tissue (thermogenesis) is important for maintaining longevity, reducing obesity and supporting energy homeostasis. Brown adipose tissue (BAT) is central to physiological energy homeostasis. Enhancing brown adipose tissue reduces obesity, diabetes, insulin resistance and non-alcoholic fatty liver..
BAT dissipates energy in the form of heat through increased theromgenesis.(1) Browning of white adipose tissue, which converts characteristics of white adipose tissue to brown adipose tissue, increases expression of the thermogenic mitochondrial protein UCP-1. The uncoupling protein 1 (UCP-1) is a potent protein which shifts energy from ATP to heat.
Greater amounts of brown adipose tissue and the thermogenic capacity of the tissue are indicative of youth. With age, brown adipose tissue is decreased, while white adipose tissue becomes predominant and accelerates aging via inflammation and insulin resistance. .
GLUCORAPHANIN - Is a precursor of sulforaphane.
In laboratory mice fed a high fat diet, glucoraphanin supplementation promoted increased energy expenditures via an increase in UCP-1 protein expression in adipose deposit areas. Furthermore, results included decreases in weight, increased insulin sensitivity and improved glucose tolerance.(2)
PTEROSTILBENE - Studied in obese rats, pterostilbene increased the thermogenic capability of the BAT through an upregulation of Ucp1 protein expression..(3)
(1) Galmozzi A, et al. ThermoMouse: an in vivo model to identify modulators of UCP1 expression in brown adipose tissue. Cell Rep. 2014. Dec.
(2) Nagata N, et al. Glucoraphanin Ameliorates Obesity and Insulin Resistance Through Adipose Tissue Browning and Reduction of Metabolic Endotoxemia in Mice. Diabetes. 2017 Feb 16.
(3) Aguirre L, et al. Effects of pterostilbene in brown adipose tissue from obese rats. J Physiol Biochem. 2017 Feb 27
In humans, there are two types of adipose tissue. White adipose tissue and brown adipose tissue. White adipose tissue is associated with excessive fat storage, obesity, insulin resistance and diabetes. Whereas, brown adipose tissue has the opposite effect - producing energy, reducing fat storage and obesity, while increasing insulin sensitivity and reducing diabetes. Further, increasing expression of brown adipose tissue (adipocytes) may also be correlated with increases in longevity.
Newborns have the greatest amount of brown fat, which helps provide a source of heat, but gradually decreases with age. Adults have a predominance of white adipose tissue which correlate with America's obesity epidemic.
BROWN ADIPOSE TISSUE
NUTRITION SUPPLEMENT SUPPORT:"Browning" of White Adipocytes.
Research indicates that fat storing white adipocytes may be altered to take on the characteristics of energy producing brown adipocytes. Such changes to white adipocytes may be an effective strategy for reducing obesity and obesity related disorders (such as insulin resistance and diabetes). Improving insulin sensitivity is a factor not only in diabetes, but also considered significant in longevity.
Improvement in number and function of mitochondria during brown fat adipogenesis. This may result in higher energy brown adipose tissue enabling even a stronger thermogenic response
(1) Inagaki T, et al. Transcriptional and epigenetic control of brown and beige adipose cell fate and function. Nat Rev Mol Cell Biol. 2016 Jun 2
(2) Qian SW, et al. BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis. Proc Natl Acad Sci USA. 2013 Feb
(3) Mookerjee SA, et al. Mitochondrial Uncoupling and Lifespan. Mech Ageing Dev. 2010 Jul - Aug.
(4) Zhang HQ, et al. Sulforaphane induces adipocyte browning and promotes glucose and lipid utilization. Mol Nutr Food Res. 2016 May 24
(5) Lone J, et al. Curcumin induces brown fat-like phenotype in 3T3-L1 and primary white adipocytes. J Nutr Biochem. 2016 Jan
(6) Ding L, et al. Andrographolide prevents high-fat diet-induced obesity in C57BL/6 mice by suppressing the sterol regulatory element-binding protein pathway. J Pharmacol Exp Ther. 2014 Nov
(7) You Y, et al. Mulberry and mulberry wine extract increase the number of mitochondria during brown adipogenesis. Food Funct. 2015 Feb
How and to what extent microbes influence on health is a relatively new area of study. Amazingly, the influence of gut microbiota on general health and longevity is only now becoming understood. Recent attention is scientific areas concern the importance of intestinal microbes and how they affect not only health of the the gut but also overall health of the body.(1) An area of keen interest is the production of Short Chain Fatty Acids (SCFAs) by microbial fermentation in the gut and how it can significantly improve health.(2)
Short Chain Fatty Acids (SCFAs - acetic acid, propionic acid and butyric acid) are produced as a fermentation byproduct of soluble fiber (e.g nuts, seeds, certain vegetables) by microbes in the large intestine.
Among the beneficial effects of SCFA's include:
THE ROLE OF TAURINE IN SHORT CHAIN FATTY ACID PRODUCTION.
Furthermore, research indicates that taurine supplementation may significantly improve the intestinal microbiotic environment by increasing the production of SCFAs and decreasing inflammatory concentrations of serum lipopolysaccharides (LPS). LPS induced inflammation is a common issue facilitated by the processed western diet.(5)
(1) Andoh A. Physiological Role of Gut Microbiota for Maintaining Human Health. Digestion. 2016 Feb 9
(2) KeenanMJ, et al. Improving healthspan via changes in gut microbiota and fermentation. Age (Dordr). 2015 Oct.
(3) Hartl FU. Cellular Homeostasis and Aging. Annu Rev Biochem. 2016 Apr 6.
(4) Puddu A, et al. Evidence for the gut microbiota short-chain fatty acids as key pathophysiological molecules improving diabetes. Mediators Inflamm. 2014
(5) Yu H, et al. Effects of taurine on gut microbiota and metabolism in mice. Amino Acids. 2016 Mar 30.