The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase. Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis. Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Hypothalamic inflammation: a double-edged sword to nutritional diseases. A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes. Minibrain/Dyrk1a regulates food intake through the Sir2-FOXO-sNPF/NPY pathway in Drosophila and mammals. Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Matching dietary amino acid balance to the in silico-translated exome optimizes growth and reproduction without cost to lifespan. Dispensable and indispensable amino acids for humans. The sequence of events leading to the establishment of the amino acid needs of man. Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women. Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. Whey protein supplementation does not alter plasma branched-chained amino acid profiles but results in unique metabolomics patterns in obese women enrolled in an 8-week weight loss trial. Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. Repletion of branched chain amino acids reverses mTORC1 signaling but not improved metabolism during dietary protein dilution. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Decreased consumption of branched-chain amino acids improves metabolic health. Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Comparing the effects of low-protein and high-carbohydrate diets and caloric restriction on brain aging in mice. Macronutrient balance, reproductive function, and lifespan in aging mice. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. The impact of low-protein high-carbohydrate diets on aging and lifespan. Obesity: the protein leverage hypothesis. Testing protein leverage in lean humans: a randomised controlled experimental study. The Nature of Nutrition: a Unifying Framework from Animal Adaption to Human Obesity (Princeton University Press, 2012). Our data highlight a role for amino acid quality in energy balance and show that health costs of chronic high BCAA intakes need not be due to intrinsic toxicity but instead are a consequence of hyperphagia driven by amino acid imbalance. Preventing hyperphagia by calorie restriction or pair-feeding averts the health costs of a high-BCAA diet. Increasing the ratio of BCAAs to these amino acids results in hyperphagia and is associated with central serotonin depletion. These effects are not due to elevated BCAA per se or hepatic mammalian target of rapamycin activation, but instead are due to a shift in the relative quantity of dietary BCAAs and other amino acids, notably tryptophan and threonine. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets leads to hyperphagia, obesity and reduced lifespan. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Nature Metabolism volume 1, pages 532–545 ( 2019) Cite this articleĮlevated branched-chain amino acids (BCAAs) are associated with obesity and insulin resistance. ![]() Branched-chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control
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