Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress-induced inflammation

Cell Rep. 2015 Jan 13;10(2):266-79. doi: 10.1016/j.celrep.2014.12.023. Epub 2015 Jan 8.

Abstract

To understand the contribution of adipose tissue fatty acid oxidation to whole-body metabolism, we generated mice with an adipose-specific knockout of carnitine palmitoyltransferase 2 (CPT2(A-/-)), an obligate step in mitochondrial long-chain fatty acid oxidation. CPT2(A-/-) mice became hypothermic after an acute cold challenge, and CPT2(A-/-) brown adipose tissue (BAT) failed to upregulate thermogenic genes in response to agonist-induced stimulation. The adipose-specific loss of CPT2 resulted in diet-dependent changes in adiposity but did not result in changes in body weight on low- or high-fat diets. Additionally, CPT2(A-/-) mice had suppressed high-fat diet-induced oxidative stress and inflammation in visceral white adipose tissue (WAT); however, high-fat diet-induced glucose intolerance was not improved. These data show that fatty acid oxidation is required for cold-induced thermogenesis in BAT and high-fat diet-induced oxidative stress and inflammation in WAT.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue, Brown / chemistry
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / chemistry
  • Adipose Tissue, White / metabolism*
  • Animals
  • Body Temperature
  • Carbohydrate Metabolism
  • Carnitine O-Palmitoyltransferase / deficiency
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Cells, Cultured
  • Diet, High-Fat
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism*
  • Inflammation
  • Iodide Peroxidase / genetics
  • Iodide Peroxidase / metabolism
  • Iodothyronine Deiodinase Type II
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Oxidation-Reduction
  • Oxidative Stress*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Thermogenesis*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Uncoupling Protein 1

Substances

  • Fatty Acids
  • Ion Channels
  • Mitochondrial Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Transcription Factors
  • Uncoupling Protein 1
  • Iodide Peroxidase
  • Carnitine O-Palmitoyltransferase