title: Loss of macrophage fatty acid oxidation does not potentiate systemic metabolic dysfunction.
abstract: 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.
authors.affiliation: Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
authors.forename: Elsie
authors.initials: E
authors.lastname: Gonzalez-Hurtado
authors.affiliation: Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
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, Maryland; and.
authors.forename: Joseph
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
authors.forename: Ebru S
authors.initials: ES
authors.lastname: Selen Alpergin
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Collins
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Maureen R
authors.initials: MR
authors.lastname: Horton
authors.affiliation: Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland; and mwolfga1@jhmi.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wolfgang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008659:Metabolic Diseases / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009765:Obesity / Q000276:immunology*; D010084:Oxidation-Reduction
chemical_list: D005227:Fatty Acids; D015847:Interleukin-4
keywords: adipose tissue; fatty acid; inflammation; macrophage; obesity