title: C/EBPα regulates macrophage activation and systemic metabolism.
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.
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California;
authors.forename: Bonggi
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California;
authors.forename: Liping
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California;
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California;
authors.forename: Hyung Sun
authors.initials: HS
authors.lastname: Yoo
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California;
authors.forename: Wai
authors.initials: W
authors.lastname: Cheung
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California;
authors.forename: Robert
authors.initials: R
authors.lastname: Mak
authors.affiliation: Department of Microbiology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado;
authors.forename: Jerome
authors.initials: J
authors.lastname: Schaack
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, California;
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Feng
authors.affiliation: Veterans Affairs San Diego Healthcare system, and Department of Medicine, University of California San Diego, La Jolla, California.
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Chi
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California;
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Olefsky
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California; jishao@ucsd.edu.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shao
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000502:physiology*; D019069:Cell Respiration / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse
keywords: CCAAT/enhancer binding protein; insulin sensitivity; macrophage; obesity