title: Muscle-specific interleukin-6 deletion influences body weight and body fat in a sex-dependent manner.
abstract: Interleukin-6 (IL-6) is a major cytokine controlling not only the immune system but also basic physiological variables such as body weight and metabolism. While central IL-6 is clearly implicated in the latter, the putative role of peripheral IL-6 controlling body weight remains unclear. We herewith report results obtained in muscle-specific IL-6 KO (mIL-6 KO) mice. mIL-6 KO male mice fed a high-fat diet (HFD, 58.4% kcal from fat) or a control diet (18%) gained less weight and body fat than littermate floxed male mice, while the opposite pattern was observed in female mice. Food intake was not affected by muscle IL-6 deficiency, but male and female mIL-6 KO mice were more and less active, respectively, in the hole-board test. Moreover, female mIL-6 KO mice did not control adequately their body temperature upon exposure to 4°C, suggesting a role of muscle IL-6 in energy expenditure. At least part of this regulatory role of muscle IL-6 may be mediated by the hypothalamus, as IL-6 deficiency regulated the expression of critical hypothalamic neuropeptides (NPY, AgRP, POMC, CRH and preproOX). Leptin and insulin changes cannot explain the phenotype of these mice. In summary, the present results demonstrate that muscle IL-6 controls body weight and body fat in a sex-specific fashion, influencing the expression of the main neuropeptides involved in energy homeostasis.
authors.affiliation: Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Ferrer
authors.affiliation: Department of Physiology, CIMUS-IDIS, University of Santiago de Compostela, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Navia
authors.affiliation: Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Giralt
authors.affiliation: Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Comes
authors.affiliation: Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Carrasco
authors.affiliation: Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain.
authors.forename: Amalia
authors.initials: A
authors.lastname: Molinero
authors.affiliation: Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Quintana
authors.affiliation: Department of Physiology, CIMUS-IDIS, University of Santiago de Compostela, Spain.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Señarís
authors.affiliation: Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain. Electronic address: Juan.Hidalgo@uab.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001833:Body Temperature Regulation; D001835:Body Weight / Q000235:genetics*; D004734:Energy Metabolism; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics*; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D009479:Neuropeptides
keywords: Body weight; High-fat diet; Hypothalamic factors; IL-6; Insulin