A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance.

Journal Article (Journal Article)

Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets. Despite having reduced food intake and a low rate of weight gain equivalent to the SC group, HF/BCAA rats were as insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1Ser307 and by accumulation of multiple acylcarnitines in muscle, and it was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance.

Full Text

Duke Authors

Cited Authors

  • Newgard, CB; An, J; Bain, JR; Muehlbauer, MJ; Stevens, RD; Lien, LF; Haqq, AM; Shah, SH; Arlotto, M; Slentz, CA; Rochon, J; Gallup, D; Ilkayeva, O; Wenner, BR; Yancy, WS; Eisenson, H; Musante, G; Surwit, RS; Millington, DS; Butler, MD; Svetkey, LP

Published Date

  • April 2009

Published In

Volume / Issue

  • 9 / 4

Start / End Page

  • 311 - 326

PubMed ID

  • 19356713

Pubmed Central ID

  • PMC3640280

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2009.02.002


  • eng

Conference Location

  • United States