Cell Metabolism
Volume 19, Issue 1, 7 January 2014, Pages 96-108
Journal home page for Cell Metabolism

Article
β-Aminoisobutyric Acid Induces Browning of White Fat and Hepatic β-Oxidation and Is Inversely Correlated with Cardiometabolic Risk Factors

https://doi.org/10.1016/j.cmet.2013.12.003Get rights and content
Under an Elsevier user license
open archive

Highlights

  • β-aminoisobutyric acid (BAIBA) is secreted from PGC-1α-expressing myocytes

  • BAIBA activates the thermogenic program in white adipocytes via PPARα

  • Circulating BAIBA levels in mice and humans are increased with exercise

  • BAIBA is inversely correlated with cardiometabolic risk factors in humans

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.

Cited by (0)