Author
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Adams, Sean |
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Submitted to: Advances in Nutrition
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/7/2011 Publication Date: 11/9/2011 Citation: Adams, S.H. 2011. Emerging perspectives on essential amino acid metabolism in obesity and the insulin-resistant states 1,2. Advances in Nutrition. doi:10.3945. Interpretive Summary: Dysregulation of insulin action is most often considered in the context of impaired glucose homeostasis, with the defining feature of diabetes mellitus being elevated blood glucose concentration. Complications arising from the hyperglycemia accompanying frank diabetes are well-known, and epidemiological studies point to higher risk toward development of metabolic disease in persons with impaired glucose tolerance. While the central role of proper blood sugar control in maintaining metabolic health is well-established, recent developments have begun to shed light on associations between compromised insulin action (obesity, pre-diabetes and type 2 diabetes mellitus [T2DM]) and altered intermediary metabolism of fats and amino acids. For amino acids, changes in blood concentrations of select essential amino acids and their derivatives--in particular branched-chain amino acids (BCAAs), sulfur amino acids, tyrosine and phenylalanine--are apparent with obesity and insulin resistance, often before the onset of clinically-diagnosed T2DM. This review provides an overview of these changes, and places recent observations from metabolomics research into the context of historical reports in the areas of biochemistry and nutritional biology. Based on this synthesis, a model is proposed that links the FFA-rich environment of obesity/insulin resistance and T2DM with diminution of BCAA catabolic enzyme activity, changes in methionine oxidation and cysteine/cystine generation, and tissue redox balance (NADH/NAD+). Technical Abstract: Dysregulation of insulin action is most often considered in the context of impaired glucose homeostasis, with the defining feature of diabetes mellitus being elevated blood glucose concentration. Complications arising from the hyperglycemia accompanying frank diabetes are well-known, and epidemiological studies point to higher risk toward development of metabolic disease in persons with impaired glucose tolerance. While the central role of proper blood sugar control in maintaining metabolic health is well-established, recent developments have begun to shed light on associations between compromised insulin action (obesity, pre-diabetes and type 2 diabetes mellitus [T2DM]) and altered intermediary metabolism of fats and amino acids. For amino acids, changes in blood concentrations of select essential amino acids and their derivatives--in particular branched-chain amino acids (BCAAs), sulfur amino acids, tyrosine and phenylalanine--are apparent with obesity and insulin resistance, often before the onset of clinically-diagnosed T2DM. This review provides an overview of these changes, and places recent observations from metabolomics research into the context of historical reports in the areas of biochemistry and nutritional biology. Based on this synthesis, a model is proposed that links the FFA-rich environment of obesity/insulin resistance and T2DM with diminution of BCAA catabolic enzyme activity, changes in methionine oxidation and cysteine/cystine generation, and tissue redox balance (NADH/NAD+). |
