Adipose Fatty Acid Oxidation Is Required for Thermogenesis and Potentiates Oxidative Stress-Induced Inflammation

• Adipose fatty acid oxidation (FAO) is required for cold-induced thermogenesis
• Adipose FAO is required for agonist-induced thermogenic gene expression
• Loss of adipose FAO does not alter body weight
• Adipose FAO is required for high-fat-induced oxidative stress and inflammation.

SummaryTo 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 (CPT2A−/−), an obligate step in mitochondrial long-chain fatty acid oxidation. CPT2A−/− mice became hypothermic after an acute cold challenge, and CPT2A−/− 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, CPT2A−/− 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.

Graphical AbstractFigure optionsDownload as PowerPoint slide