title: Glucocorticoids increase adipocytes in muscle by affecting IL-4 regulated FAP activity.
abstract: An increase in intramuscular adipocyte tissue (IMAT) is associated with glucose dysregulation, decreased muscle strength, and increased risk of disability. Unfortunately, the mechanisms stimulating intramuscular adipogenesis remain unclear. We found that dexamethasone (Dex) administration to mice with injured muscles stimulates the accumulation of IMAT. To identify precursors of these adipocytes, we isolated satellite cells and fibro/adipogenic progenitors (FAPs) from muscle; satellite cells did not differentiate into adipocytes even following Dex treatment. In contrast, Dex stimulated FAP differentiation into adipocytes. In vivo, we transplanted purified FAPs from transgenic, EGFP mice into the injured muscles of C57/BL6 mice and found that Dex administration stimulated adipogenesis from FAP-EGFP. The increase in adipogenesis depended on Dex-induced inhibition of interleukin-4 (IL-4). In the injured muscle of IL-4-knockout mice, the levels of adipocytes were increased, while in the injured muscles of Dex-treated mice with IL-4 injections, adipogenesis was suppressed. In cultured FAPs, IL-4 inhibited Dex-induced conversion of FAPs into adipocytes; this did not occur in FAPs expressing knockdown of the IL-4 receptor. Thus, we concluded that glucocorticoids stimulate FAPs to differentiate into adipocytes in injured muscles. This process is blocked by IL-4, suggesting that interfering with IL-4 signaling could prevent adipogenesis in muscle.
authors.affiliation: Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA; Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China; and.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA; Nephrology Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Kleiton Augusto Santos
authors.initials: KA
authors.lastname: Silva
authors.affiliation: Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA;
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA; lipingz@bcm.edu.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D015847:Interleukin-4 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D003907:Dexamethasone
keywords: dexamethasone; progenitors