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

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

Author information

1
Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
2
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
3
Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland; and mwolfga1@jhmi.edu.

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.

KEYWORDS:

adipose tissue; fatty acid; inflammation; macrophage; obesity

PMID:
28223293
PMCID:
PMC5451524
DOI:
10.1152/ajpendo.00408.2016
[Indexed for MEDLINE]
Free PMC Article

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