| First Author | Lee B | Year | 2014 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 306 |
| Issue | 10 | Pages | E1144-54 |
| PubMed ID | 24691027 | Mgi Jnum | J:213166 |
| Mgi Id | MGI:5582993 | Doi | 10.1152/ajpendo.00002.2014 |
| Citation | Lee B, et al. (2014) C/EBPalpha regulates macrophage activation and systemic metabolism. Am J Physiol Endocrinol Metab 306(10):E1144-54 |
| abstractText | Macrophage infiltration plays an important role in obesity-induced insulin resistance. CCAAT enhancer-binding protein-alpha (C/EBPalpha) is a transcription factor that is highly expressed in macrophages. To examine the roles of C/EBPalpha in regulating macrophage functions and energy homeostasis, macrophage-specific C/EBPalpha knockout (MalphaKO) mice were created. Chow-fed MalphaKO 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 MalphaKO mice, systemic insulin sensitivity was protected during HF-feeding due to preserved insulin sensitivity in skeletal muscle. We also found that C/EBPalpha-deficient macrophages exhibited a blunted response of cytokine-induced expression of M1 and M2 macrophage markers, suggesting that C/EBPalpha 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 MalphaKO mice. Furthermore, expression levels of inflammatory cytokines were reduced in skeletal muscle of HF-fed MalphaKO mice. Together, these results imply that C/EBPalpha is required for macrophage activation, which plays an important role in maintaining skeletal muscle energy metabolism. |
