β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors.

Roberts LD, Boström P, O'Sullivan JF, Schinzel RT, Lewis GD, Dejam A, Lee YK, Palma MJ, Calhoun S, Georgiadi A, Chen MH, Ramachandran VS, Larson MG, Bouchard C, Rankinen T, Souza AL, Clish CB, Wang TJ, Estall JL, Soukas AA, Cowan CA, Spiegelman BM, Gerszten RE
Cell Metab. 2014 19 (1): 96-108

PMID: 24411942 · PMCID: PMC4017355 · DOI:10.1016/j.cmet.2013.12.003

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) regulates metabolic genes in skeletal muscle and contributes to the response of muscle to exercise. Muscle PGC-1α transgenic expression and exercise both increase the expression of thermogenic genes within white adipose. How the PGC-1α-mediated response to exercise in muscle conveys signals to other tissues remains incompletely defined. We employed a metabolomic approach to examine metabolites secreted from myocytes with forced expression of PGC-1α, and identified β-aminoisobutyric acid (BAIBA) as a small molecule myokine. BAIBA increases the expression of brown adipocyte-specific genes in white adipocytes and β-oxidation in hepatocytes both in vitro and in vivo through a PPARα-mediated mechanism, induces a brown adipose-like phenotype in human pluripotent stem cells, and improves glucose homeostasis in mice. In humans, plasma BAIBA concentrations are increased with exercise and inversely associated with metabolic risk factors. BAIBA may thus contribute to exercise-induced protection from metabolic diseases.

Copyright © 2014 Elsevier Inc. All rights reserved.

MeSH Terms (26)

Adipocytes, Brown Adipocytes, White Adipose Tissue, Brown Adipose Tissue, White Aminoisobutyric Acids Animals Cardiovascular Diseases Cell Differentiation Exercise Gene Expression Regulation Glucose Tolerance Test Humans Induced Pluripotent Stem Cells Liver Metabolic Diseases Mice Organ Specificity Oxidation-Reduction Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Phenotype Physical Conditioning, Animal PPAR alpha Risk Factors Transcription, Genetic Transcription Factors Weight Gain

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