Isoleucine or valine deprivation stimulates fat loss via increasing energy expenditure and regulating lipid metabolism in WAT

Du, Ying; Meng, Qingshu; Zhang, Qian; Guo, Feifan

doi:10.1007/s00726-011-1123-8

Cited by 99 publications

(89 citation statements)

References 54 publications

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“…This is consistent with a previous report of BAT UCP-1 expression in mice exposed to 7 days of leucine-deficient diet (6), as well as a study of mice exposed to VDD for 7 days (but lacking a PF control group) (11). Several studies provide evidence of a link between central melanocortin signaling and activation of BAT (3,39).…”

Section: Discussionsupporting

confidence: 92%

Hypothalamic signaling in anorexia induced by indispensable amino acid deficiency

Zhu

Krasnow

Roth-Carter

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Section: Discussionsupporting

confidence: 92%

Hypothalamic signaling in anorexia induced by indispensable amino acid deficiency

Zhu

Krasnow

Roth-Carter

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…Regarding BCAAs values, only isoleucine serum levels significantly decreased. Existing evidence suggests that the reduction in isoleucine levels promote lipolysis via induction of lipolytic genes and by the suppression of lipogenesis in liver [11].…”

Section: Discusionmentioning

confidence: 99%

Metabolomics identifies changes in fatty acid and amino acid profiles in serum of overweight older adults following a weight loss intervention

et al. 2014

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3 AbstractThe application of metabolomics in nutritional research may be a useful tool to analyse and predict the response to a dietary intervention. The aim of this study was to examine metabolic changes in serum samples following exposure to an energy-restricted diet (-15% of daily energy requirements) over a period of 8 weeks in overweight and obese older adults (n=22) using a GC/MS metabolomic approach. After the 8 weeks, there were significant reductions in weight (7%) and metabolic improvement (glucose and lipid profile). Metabolomic analysis found that total saturated fatty acids (SFAs), including palmitic acid (C16:0) and stearic acid (C18:0) and monounsaturated fatty acids (MUFAs) were significantly decreased after the 8 week intervention.Furthermore, palmitoleic acid (C16:1) was found to be a negative predictor of change in body fat loss. Both the total ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) significantly decreased although the overall total amounts of PUFAs did not. The branched chain amino acid (BCAA) isoleucine significantly decreased in the serum samples after the intervention. In conclusion, this study demonstrated that the weight loss intervention based on a hypocaloric diet identified changes in the metabolic profiles of serum in overweight and obese older adults, with a reduction in anthropometric and biochemical parameters also found.

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“…45 On the other hand, deprivation of a single or all three BCAAs improves insulin sensitivity and glycemic control in either chow-or High-Fat Diet (HFD)-fed, or genetically diabetic rodents. [46][47][48] These findings strongly indicate not only a correlative, but also a causative role of circulating BCAAs and their oxidized intermediates in the development of insulin resistance and diabetes. As such, it is important to advance our understanding of BCAA regulatory mechanisms that would allow us to explain the reasons for high circulating levels of BCAAs found in obese and diabetic individuals.…”

mentioning

confidence: 80%

Are BCAAs Mere Biomarkers of Diabetes?

Shin¹

2017

Diabetes Res Open J

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Branched-chain amino acids (BCAAs; ie. leucine, isoleucine, and valine) are essential amino acids we need to ingest through our diet.While circulating BCAA levels were first found to be elevated in obese individuals back in 1969 by Felig and colleagues, 1 the potential role of BCAAs in obesity and diabetes development has been re-highlighted in the last decade. Using advanced metabolomic platforms, many independent investigators were able to reproduce the earlier finding and further demonstrate that not only plasma BCAAs, but also their partially oxidized intermediates such as α-keto acids and short-chain (C3-C5) acylcarnitines are increased in obese or insulin resistant/diabetic individuals, including Caucasians and Asians. 2-9Moreover, plasma BCAAs are found to be the earliest and the most predictive marker for future risk of diabetes, 10 and elevated plasma leucine levels precede the development of fatty liver, 11suggesting that circulating leucine is a predictive marker of hepatic steatosis. Interestingly, plasma BCAAs and their derived short-chain acylcarnitines are effectively lowered by bariatric surgery in obese and/or diabetic individuals. 5,8,12,13 Whether this normalized BCAA metabolism after RYGB surgery in morbidly obese patients contributes to improved insulin sensitivity and glycemic control or is just a secondary effect of the surgery needs to be examined further. Nonetheless, collectively these studies implicate a role of plasma BCAAs and their metabolites in the pathogenesis of insulin resistance and diabetes.The unresolved question in the field today is whether or not they are mere biomarkers or they are one of the potential culprits for derangement of glucose metabolism and development of obesity and insulin resistance/diabetes. While a number of studies demonstrate that either amino acid mixture or BCAA supplementation have beneficial effects on protein turnover and muscle wasting in patients with cirrhosis, kidney failure, cancer, or sepsis, [14][15][16][17][18][19][20][21][22][23][24][25] mounting evidence suggests that amino acids/BCAAs or their metabolized keto acids lead to hyperactivation of mTOR signaling, 7,26-28 induction of oxidative stress, 29-32 mitochondrial dysfunction, 33,34 apoptosis, 35,36 and more importantly, insulin resistance and/or impaired glucose metabolism. 7,[26][27][28][37][38][39][40][41][42][43][44] Consistent with these findings, recent studies demonstrate that a BCAA metabolite elevated in diabetic individuals can drive vascular fatty acid transport in muscle and induce insulin resistance in mice 44 and a defective muscle BCAA metabolism induces impaired lipid metabolism and insulin resistance.45 On the other hand, deprivation of a single or all three BCAAs improves insulin sensitivity and glycemic control in either chow-or High-Fat Diet (HFD)-fed, or genetically diabetic rodents.46-48 These findings strongly indicate not only a correlative, but also a causative role of circulating BCAAs and their oxidized intermediates in the development of insulin resistance ...

show abstract

Isoleucine or valine deprivation stimulates fat loss via increasing energy expenditure and regulating lipid metabolism in WAT

Cited by 99 publications

References 54 publications

Hypothalamic signaling in anorexia induced by indispensable amino acid deficiency

Hypothalamic signaling in anorexia induced by indispensable amino acid deficiency

Metabolomics identifies changes in fatty acid and amino acid profiles in serum of overweight older adults following a weight loss intervention

Are BCAAs Mere Biomarkers of Diabetes?

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