Loss of macrophage fatty acid oxidation does not potentiate systemic metabolic dysfunction

Am J Physiol Endocrinol Metab. 2017 May 1;312(5):E381-E393. doi: 10.1152/ajpendo.00408.2016. Epub 2017 Feb 21.


Fatty acid oxidation in macrophages has been suggested to play a causative role in high-fat diet-induced metabolic dysfunction, particularly in the etiology of adipose-driven insulin resistance. To understand the contribution of macrophage fatty acid oxidation directly to metabolic dysfunction in high-fat diet-induced obesity, we generated mice with a myeloid-specific knockout of carnitine palmitoyltransferase II (CPT2 Mϕ-KO), an obligate step in mitochondrial long-chain fatty acid oxidation. While fatty acid oxidation was clearly induced upon IL-4 stimulation, fatty acid oxidation-deficient CPT2 Mϕ-KO bone marrow-derived macrophages displayed canonical markers of M2 polarization following IL-4 stimulation in vitro. In addition, loss of macrophage fatty acid oxidation in vivo did not alter the progression of high-fat diet-induced obesity, inflammation, macrophage polarization, oxidative stress, or glucose intolerance. These data suggest that although IL-4-stimulated alternatively activated macrophages upregulate fatty acid oxidation, fatty acid oxidation is dispensable for macrophage polarization and high-fat diet-induced metabolic dysfunction. Macrophage fatty acid oxidation likely plays a correlative, rather than causative, role in systemic metabolic dysfunction.

Keywords: adipose tissue; fatty acid; inflammation; macrophage; obesity.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Diet, High-Fat
  • Fatty Acids / immunology*
  • Interleukin-4 / immunology*
  • Macrophage Activation / immunology*
  • Macrophages / immunology*
  • Male
  • Metabolic Diseases / immunology*
  • Metabolic Diseases / pathology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Obesity / immunology*
  • Oxidation-Reduction


  • Fatty Acids
  • Interleukin-4