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Am J Physiol Endocrinol Metab. 2014 May 15;306(10):E1144-54. doi: 10.1152/ajpendo.00002.2014. Epub 2014 Apr 1.

C/EBPα regulates macrophage activation and systemic metabolism.

Author information

1
Department of Pediatrics, University of California San Diego, La Jolla, California;
2
Department of Medicine, University of California San Diego, La Jolla, California;
3
Department of Microbiology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado;
4
Department of Pathology, University of California San Diego, La Jolla, California;
5
Veterans Affairs San Diego Healthcare system, and Department of Medicine, University of California San Diego, La Jolla, California.
6
Department of Pediatrics, University of California San Diego, La Jolla, California; jishao@ucsd.edu.

Abstract

Macrophage infiltration plays an important role in obesity-induced insulin resistance. CCAAT enhancer-binding protein-α (C/EBPα) is a transcription factor that is highly expressed in macrophages. To examine the roles of C/EBPα in regulating macrophage functions and energy homeostasis, macrophage-specific C/EBPα knockout (MαKO) mice were created. Chow-fed MαKO mice exhibited higher body fat mass and decreased energy expenditure despite no change in food intake. However, the obese phenotype disappeared after high-fat (HF) diet feeding. Although there was a transient decrease in insulin sensitivity of chow-fed young MαKO mice, systemic insulin sensitivity was protected during HF-feeding due to preserved insulin sensitivity in skeletal muscle. We also found that C/EBPα-deficient macrophages exhibited a blunted response of cytokine-induced expression of M1 and M2 macrophage markers, suggesting that C/EBPα controls both M1 and M2 polarization. Consistent with decreased exercise capacity, mitochondrial respiration rates and signal pathways for fatty acid oxidation were remarkably reduced in the skeletal muscle of chow-fed MαKO mice. Furthermore, expression levels of inflammatory cytokines were reduced in skeletal muscle of HF-fed MαKO mice. Together, these results imply that C/EBPα is required for macrophage activation, which plays an important role in maintaining skeletal muscle energy metabolism.

KEYWORDS:

CCAAT/enhancer binding protein; insulin sensitivity; macrophage; obesity

PMID:
24691027
PMCID:
PMC4025063
DOI:
10.1152/ajpendo.00002.2014
[Indexed for MEDLINE]
Free PMC Article

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