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.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • PPAR alpha / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Phenotype
  • Physical Conditioning, Animal
  • Risk Factors
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects
  • Weight Gain / drug effects

Substances

  • Aminoisobutyric Acids
  • PPAR alpha
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Transcription Factors
  • 3-aminoisobutyric acid