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

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 ge...

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Bibliographic Details
Published in:	Cell metabolism Vol. 19; no. 1; p. 96
Main Authors:	Roberts, Lee D, Boström, Pontus, O'Sullivan, John F, Schinzel, Robert T, Lewis, Gregory D, Dejam, Andre, Lee, Youn-Kyoung, Palma, Melinda J, Calhoun, Sondra, Georgiadi, Anastasia, Chen, Ming-Huei, Ramachandran, Vasan S, Larson, Martin G, Bouchard, Claude, Rankinen, Tuomo, Souza, Amanda L, Clish, Clary B, Wang, Thomas J, Estall, Jennifer L, Soukas, Alexander A, Cowan, Chad A, Spiegelman, Bruce M, Gerszten, Robert E
Format:	Journal Article
Language:	English
Published:	United States 07.01.2014
Subjects:	Adipocytes, Brown - drug effects Adipocytes, Brown - metabolism Adipocytes, Brown - pathology Adipocytes, White - drug effects Adipocytes, White - metabolism Adipocytes, White - pathology Adipose Tissue, Brown - cytology Adipose Tissue, Brown - drug effects Adipose Tissue, Brown - metabolism Adipose Tissue, White - cytology Adipose Tissue, White - drug effects Adipose Tissue, White - metabolism Aminoisobutyric Acids - blood Aminoisobutyric Acids - pharmacology Animals Cardiovascular Diseases - metabolism Cardiovascular Diseases - pathology Cell Differentiation - drug effects Exercise Gene Expression Regulation - drug effects Glucose Tolerance Test Humans Induced Pluripotent Stem Cells - drug effects Induced Pluripotent Stem Cells - metabolism Liver - drug effects Liver - metabolism Metabolic Diseases - metabolism Metabolic Diseases - pathology Mice Organ Specificity - drug effects Organ Specificity - genetics Oxidation-Reduction - drug effects Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Phenotype Physical Conditioning, Animal PPAR alpha - metabolism Risk Factors Transcription Factors - metabolism Transcription, Genetic - drug effects Weight Gain - drug effects
ISSN:	1932-7420, 1932-7420
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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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1932-7420 1932-7420
DOI:	10.1016/j.cmet.2013.12.003