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Cell Metab DOI:10.1016/j.cmet.2013.12.003

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

Publication TypeJournal Article
Year of Publication2014
AuthorsRoberts, LD, Boström, P, O'Sullivan, JF, Schinzel, RT, Lewis, GD, Dejam, A, Lee, Y-K, Palma, MJ, Calhoun, S, Georgiadi, A, Chen, M-H, Ramachandran, VS, Larson, MG, Bouchard, C, Rankinen, T, Souza, AL, Clish, CB, Wang, TJ, Estall, JL, Soukas, AA, Cowan, CA, Spiegelman, BM, Gerszten, RE
JournalCell Metab
Date Published2014 Jan 07
KeywordsAdipocytes, Brown, Adipocytes, White, Adipose Tissue, Brown, Adipose Tissue, White, Aminoisobutyric Acids, Animals, Cardiovascular Diseases, Cell Differentiation, Exercise, Gene Expression Regulation, Glucose Tolerance Test, Humans, Induced Pluripotent Stem Cells, Liver, Metabolic Diseases, Mice, Organ Specificity, Oxidation-Reduction, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Phenotype, Physical Conditioning, Animal, PPAR alpha, Risk Factors, Transcription Factors, Transcription, Genetic, Weight Gain

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.


Alternate JournalCell Metab.
PubMed ID24411942
PubMed Central IDPMC4017355
Grant ListN01-HC-25195 / HC / NHLBI NIH HHS / United States
DK 31405 / DK / NIDDK NIH HHS / United States
R01 DK081572 / DK / NIDDK NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
R01 HL098280 / HL / NHLBI NIH HHS / United States
R01-HL045670 / HL / NHLBI NIH HHS / United States
R37 DK031405 / DK / NIDDK NIH HHS / United States
R01 DK095384 / DK / NIDDK NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 DK031405 / DK / NIDDK NIH HHS / United States
R01 HL045670 / HL / NHLBI NIH HHS / United States