Abstract 15983: Beta-Aminoisobutyric Acid Increases Browning of White Fat and is Inversely Correlated with Cardiometabolic Risk Factors in Humans
The transcriptional co-activator peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1α) regulates metabolic gene programs in skeletal muscle, and contributes substantially to the response of muscle to exercise. Muscle specific PGC-1α transgenic expression and exercise both increase expression of brown adipocyte-specific genes within white adipose depots, enhancing the oxidative activity of this tissue. How the PGC-1α mediated response to exercise in skeletal muscle conveys signals to other tissues remains incompletely defined. The discovery of the PGC-1α-dependent myokine, irisin, establishes one mechanism for signaling from muscle to white adipose tissue during exercise. We employed a metabolic profiling approach to examine non-protein small molecule metabolites secreted from myocytes with forced expression of PGC-1α, and identified β-aminoisobutyric acid (BAIBA) as a novel small molecule myokine signal. BAIBA induces expression of brown adipocyte-specific genes in white adipose tissue both in vitro and in vivo, and improves glucose homeostasis in mice. Exposure of human induced pluripotent stem cells to BAIBA during differentiation to adipocytes increases the expression of brown adipocyte-specific genes, leading to a brown adipose-like phenotype characterized by increased basal and insulin stimulated glucose uptake and increased oxygen consumption. In humans, plasma concentrations of BAIBA are increased with regular exercise and inversely associated with metabolic risk factors. BAIBA may thus contribute to exercise-induced protection from metabolic diseases.
- © 2012 by American Heart Association, Inc.