title: Exercise-mediated IL-6 signaling occurs independent of inflammation and is amplified by training in mouse adipose tissue.
abstract: The purpose of this investigation was to determine whether exercise-induced increases in adipose tissue interleukin 6 (IL-6) signaling occurred as part of a larger proinflammatory response to exercise and whether the induction of IL-6 signaling with acute exercise was altered in trained mice in parallel with changes in the IL-6 receptor complex. Sedentary and trained C57BL/6J mice were challenged with an acute bout of exercise. Adipose tissue and plasma were collected immediately and 4 h afterward and analyzed for changes in indices of IL-6 signaling, circulating IL-6, markers of adipose tissue inflammation, and expression/content of IL-6 receptor and glycoprotein 130 (gp130). In untrained mice, IL-6 mRNA increased immediately after exercise, and increases in indices of IL-6 signaling were increased 4 h after exercise in epididymal, but not inguinal adipose tissue. This occurred independent of increases in plasma IL-6 and alterations in markers of inflammation. When compared with untrained mice, in trained mice, acute exercise induced the expression of gp130 and IL-6 receptor alpha (IL-6Rα), and training increased the protein content of these. Acute exercise induced the expression, and training increased the protein content, of glycoprotein 130 and IL-6Rα and was associated with a more rapid increase in markers of IL-6 signaling in epididymal adipose tissue from trained compared with untrained mice. The ability of exogenous IL-6 to increase phosphorylation of STAT3 was similar between groups. Our findings demonstrate that acute exercise increases IL-6 signaling in a depot-dependent manner, likely through an autocrine/paracrine mechanism. This response is initiated more rapidly after exercise in trained mice, potentially as a result of increases in IL-6Rα and gp130.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and.
authors.forename: Laura
authors.initials: L
authors.lastname: Castellani
authors.affiliation: Faculty of Health, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.
authors.forename: Christopher G R
authors.initials: CG
authors.lastname: Perry
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and.
authors.forename: Rebecca E K
authors.initials: RE
authors.lastname: Macpherson
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and.
authors.forename: Jared
authors.initials: J
authors.lastname: Root-McCaig
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Huber
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Arkell
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Simpson
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and dcwright@uoguelph.ca.
authors.forename: David C
authors.initials: DC
authors.lastname: Wright
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007249:Inflammation / Q000503:physiopathology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D005082:Physical Exertion; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor / Q000378:metabolism; D057185:Sedentary Behavior; D015398:Signal Transduction
chemical_list: D005230:Fatty Acids, Nonesterified; C494200:Il6st protein, mouse; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C113250:interleukin-6 receptor alpha; C577686:interleukin-6, mouse; D050822:Cytokine Receptor gp130
keywords: IL-6; adipose tissue; exercise; inflammation; mice