Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.

ABSTRACT:

Objective

Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear.

Methods

To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis.

Results

Our data demonstrate perturbed BCAA metabolism and fatty acid

SUBMITTER: Lerin C 

PROVIDER: S-EPMC5034611 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature