title: Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress-induced inflammation.
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.
authors.affiliation: Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jieun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Ellis
authors.affiliation: Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: mwolfga1@jhmi.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wolfgang
mesh_terms: D002001:Adipose Tissue, Brown / Q000737:chemistry / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001831:Body Temperature; D050260:Carbohydrate Metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D007249:Inflammation; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D022722:Thermogenesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D002334:Carnitine O-Palmitoyltransferase; D005227:Fatty Acids; D007453:Iodide Peroxidase; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II; C485290:Ppargc1a protein, mouse