Muscle-Liver Trafficking of BCAA-Derived Nitrogen Underlies Obesity-Related Glycine Depletion.

Journal Article (Journal Article)

Glycine levels are inversely associated with branched-chain amino acids (BCAAs) and cardiometabolic disease phenotypes, but biochemical mechanisms that explain these relationships remain uncharted. Metabolites and genes related to BCAA metabolism and nitrogen handling were strongly associated with glycine in correlation analyses. Stable isotope labeling in Zucker fatty rats (ZFRs) shows that glycine acts as a carbon donor for the pyruvate-alanine cycle in a BCAA-regulated manner. Inhibition of the BCAA transaminase (BCAT) enzymes depletes plasma pools of alanine and raises glycine levels. In high-fat-fed ZFRs, dietary glycine supplementation raises urinary acyl-glycine content and lowers circulating triglycerides but also results in accumulation of long-chain acyl-coenzyme As (acyl-CoAs), lower 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in muscle, and no improvement in glucose tolerance. Collectively, these studies frame a mechanism for explaining obesity-related glycine depletion and also provide insight into the impact of glycine supplementation on systemic glucose, lipid, and amino acid metabolism.

Full Text

Duke Authors

Cited Authors

  • White, PJ; Lapworth, AL; McGarrah, RW; Kwee, LC; Crown, SB; Ilkayeva, O; An, J; Carson, MW; Christopher, BA; Ball, JR; Davies, MN; Kjalarsdottir, L; George, T; Muehlbauer, MJ; Bain, JR; Stevens, RD; Koves, TR; Muoio, DM; Brozinick, JT; Gimeno, RE; Brosnan, MJ; Rolph, TP; Kraus, WE; Shah, SH; Newgard, CB

Published Date

  • November 10, 2020

Published In

Volume / Issue

  • 33 / 6

Start / End Page

  • 108375 -

PubMed ID

  • 33176135

Pubmed Central ID

  • PMC8493998

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2020.108375


  • eng

Conference Location

  • United States