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

Lee D. Roberts, Pontus Boström, John F. O'Sullivan, Robert T. Schinzel, Gregory D. Lewis, Andre Dejam, Youn Kyoung Lee, Melinda J. Palma, Sondra Calhoun, Anastasia Georgiadi, Ming Huei Chen, Vasan S. Ramachandran, Martin G. Larson, Claude Bouchard, Tuomo Rankinen, Amanda L. Souza, Clary B. Clish, Thomas J. Wang, Jennifer L. Estall, Alexander A. SoukasChad A. Cowan, Bruce M. Spiegelman, Robert E. Gerszten

Research output: Contribution to journalArticle

262 Scopus citations

Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)96-108
Number of pages13
JournalCell Metabolism
Volume19
Issue number1
DOIs
StatePublished - Jan 7 2014
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Roberts, L. D., Boström, P., O'Sullivan, J. F., Schinzel, R. T., Lewis, G. D., Dejam, A., Lee, Y. K., Palma, M. J., Calhoun, S., Georgiadi, A., Chen, M. H., Ramachandran, V. S., Larson, M. G., Bouchard, C., Rankinen, T., Souza, A. L., Clish, C. B., Wang, T. J., Estall, J. L., ... Gerszten, R. E. (2014). β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metabolism, 19(1), 96-108. https://doi.org/10.1016/j.cmet.2013.12.003