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

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• 作者：Lee聽D. Roberts ; Pontus Bostr枚m ; John聽F. O鈥橲ullivan ; Robert聽T. Schinzel ; Gregory聽D. Lewis ; Andre Dejam ; Youn-Kyoung Lee ; Melinda聽J. Palma ; Sondra Calhoun ; Anastasia Georgiadi ; Ming-Huei Chen ; Vasan聽S. Ramach ; ran ; Martin聽G. Larson ; Claude Bouchard ; Tuomo Rankinen ; Am ; a聽L. Souza ; Clary聽B. Clish ; Thomas聽J. Wang ; Jennifer聽L. Estall ; Alex ; er聽A. Soukas ; Chad聽A. Cowan ; et al.
• 刊名：Cell Metabolism
• 出版年：7 January, 2014
• 年：2014
• 卷：19
• 期：1
• 页码：96-108
• 全文大小：1362 K

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Summary

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1伪 (PGC-1伪) regulates metabolic genes in skeletal muscle and contributes to the response of muscle to exercise. Muscle PGC-1伪 transgenic expression and exercise both increase the expression of thermogenic genes within white adipose. How the PGC-1伪-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-1伪, and identified 尾-aminoisobutyric acid (BAIBA) as a small molecule myokine. BAIBA increases the expression of brown adipocyte-specific genes in white adipocytes and 尾-oxidation in hepatocytes both in聽vitro and in聽vivo through a PPAR伪-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.