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

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

  • Cell Metab. 2014 Jan 7;19(1):96-108. doi: 10.1016/j.cmet.2013.12.003.
Lee D Roberts 1,  Pontus Boström 2,  John F O'Sullivan 1,  Robert T Schinzel 3,  Gregory D Lewis 4,  Andre Dejam 1,  Youn-Kyoung Lee 5,  Melinda J Palma 1,  Sondra Calhoun 6,  Anastasia Georgiadi 7,  Ming-Huei Chen 8,  Vasan S Ramachandran 9,  Martin G Larson 10,  Claude Bouchard 11,  Tuomo Rankinen 11,  Amanda L Souza 12,  Clary B Clish 12,  Thomas J Wang 13,  Jennifer L Estall 14,  Alexander A Soukas 15,  Chad A Cowan 16,  Bruce M Spiegelman 6,  Robert E Gerszten 17
Affiliations

Affiliations

  • 1 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • 2 Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, MA 02115, USA; Institutionen för Cell-Och Molekylärbiologi (CMB), Karolinska Institutet, von Eulers väg 3, 171 77 Stockholm, Sweden.
  • 3 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Institut für Biologie-Mikrobiologie, Fachbereich Biologie, Chemie, Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 12-16,14195 Berlin, Germany.
  • 4 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 5 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • 6 Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, MA 02115, USA.
  • 7 Institutionen för Cell-Och Molekylärbiologi (CMB), Karolinska Institutet, von Eulers väg 3, 171 77 Stockholm, Sweden.
  • 8 Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA 01702, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
  • 9 Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA 01702, USA; Cardiology Section, Boston Medical Center, Boston University School of Medicine, Boston, MA 02118, USA.
  • 10 Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA 01702, USA; Department of Mathematics and Statistics, Boston University, Boston, MA 02215, USA.
  • 11 Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
  • 12 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 13 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Cardiology Division, Vanderbilt University, Nashville, TN 37232, USA.
  • 14 Institut de Recherches Cliniques de Montreal, Montreal, QC H2W 1R7, Canada.
  • 15 Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • 16 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • 17 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: [email protected].
PMID: 24411942 DOI: 10.1016/j.cmet.2013.12.003
Abstract

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.

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