title: IL-17 inhibits adipogenesis in part via C/EBPα, PPARγ and Krüppel-like factors.
abstract: IL-17 is an inflammatory cytokine associated with anti-microbial host defense and pathogenesis of autoimmune diseases. Obesity is considered to be an inflammatory condition, but how cytokines and fat metabolism are interconnected remains poorly understood. Mesenchymal stem cells can differentiate into adipocytes, which serve as depots for stored fat. Despite the pro-inflammatory properties of IL-17, both IL-17- and IL-17RA-deficient mice are overweight. Consistently, IL-17 suppresses maturation of cells with adipogenic potential. However, the mechanism underlying IL-17-mediated inhibition is not defined. In this study, we addressed this question by evaluating the impact of IL-17 on a variety of transcription factors (TFs) that control adipogenesis, using 3T3-L1 cells to model adipocyte differentiation. Surprisingly, IL-17 does not suppress adipogenesis via C/EBPβ and C/EBPδ, TFs often considered to be central regulators of adipogenesis. Rather, IL-17 suppresses expression of several pro-adipogenic TFs, including PPARγ and C/EBPα. Moreover, we found that IL-17 regulates expression of several members of the Krüppel-like family (KLF). Specifically, IL-17 suppresses KLF15, a pro-adipogenic TF, and enhances expression of KLF2 and KLF3, which are anti-adipogenic. Thus, IL-17 suppresses adipogenesis at least in part through the combined effects of TFs that regulate adipocyte differentiation.
authors: University of Pittsburgh, Division of Rheumatology and Clinical Immunology, Pittsburgh, PA 15261, USA.
authors: Mushtaq
authors: M
authors: Ahmed
authors: Sarah L
authors: SL
authors: Gaffen
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D004742:Enhancer Elements, Genetic / Q000235:genetics; D020381:Interleukin-17 / Q000494:pharmacology*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000378:metabolism
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D020381:Interleukin-17; D051741:Kruppel-Like Transcription Factors; D047495:PPAR gamma; D011965:Receptors, Glucocorticoid