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Interplay between lipids and branched-chain amino acids in development of insulin resistance

by Christopher B Newgard

Abstract: SummaryFatty acids (FA) and FA-derived metabolites have long been implicated in the development of insulin resistance and type 2 diabetes. Surprisingly, application of metabolomics technologies has revealed that branched-chain amino acids (BCAA) and related metabolites are more strongly associated with insulin resistance than many common lipid species. Moreover, the BCAA-related signature is predictive of incident diabetes and intervention outcomes, and uniquely responsive to therapeutic interventions. Nevertheless, in animal feeding studies, BCAA supplementation requires the background of a high-fat diet to promote insulin resistance. This article develops a model to explain how lipids and BCAA may synergize to promote metabolic diseases.
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The article reviews the literature about the Randle cycle and mitochondrial inertia, and develops a model to explain how lipids and BCAAs play together to promote insulin resistance. A literature review shows that BCAAs are associated with insulin resistance and diabetes more than any other metabolite studied. Yet the negative effects of BCAAs only seem to show up in "high-fat" diets. The authors therefore believe that BCAAs can "clog up" the TCA cycle similarly to lipids, possibly competing for similar pathways. This can then lead to glucose intolerance.

Original source: https://pmc.ncbi.nlm.nih.gov/articles/PMC3695706/