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      Emerging perspectives on essential amino acid metabolism in obesity and the insulin-resistant state.

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      Advances in nutrition (Bethesda, Md.)
      American Society for Nutrition

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          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. Although 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, prediabetes, 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 BCAA, 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+).

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          Author and article information

          Journal
          Adv Nutr
          Advances in nutrition (Bethesda, Md.)
          American Society for Nutrition
          2156-5376
          2161-8313
          Nov 2011
          : 2
          : 6
          Affiliations
          [1 ] Obesity and Metabolism Research Unit, USDA Agricultural Research Service Western Human Nutrition Research Center, and Department of Nutrition, University of California, Davis, CA, USA. sean.h.adams@ars.usda.gov
          Article
          000737
          10.3945/an.111.000737
          3226382
          22332087
          a959e981-4acd-4807-9c0c-910f13e675ce

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