A Branched-chain Amino Acid-related Metabolic Signature That Differentiates Obese and Lean Humans and Contributes to Insulin Resistance

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2009 Apr 10

PMID 19356713

Citations 1605

Authors

Christopher B Newgard

Jie An

James R Bain

Michael J Muehlbauer

Robert D Stevens

Lillian F Lien

Andrea M Haqq

Svati H Shah

Michelle Arlotto

Cris A Slentz

James Rochon

Dianne Gallup

Olga Ilkayeva

Brett R Wenner

William S Yancy Jr

Howard Eisenson

Gerald Musante

Richard S Surwit

David S Millington

Mark D Butler

Laura P Svetkey

Affiliations

Soon will be listed here.

Abstract

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.

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