TY - JOUR
T1 - Muscle-specific interleukin-6 deletion influences body weight and body fat in a sex-dependent manner
AU - Ferrer, Beatriz
AU - Navia, Belén
AU - Giralt, Mercedes
AU - Comes, Gemma
AU - Carrasco, Javier
AU - Molinero, Amalia
AU - Quintana, Albert
AU - Señarís, Rosa M.
AU - Hidalgo, Juan
N1 - Funding Information:
The studies were supported by the European Commission FP6 Integrated Project Exgenesis (Ref. LSHM-CT-2004-005272), SAF2008-00435 and SAF2011-23272 (J.H.); and by Xunta de Galicia (R.S.).
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Body weight
KW - High-fat diet
KW - Hypothalamic factors
KW - IL-6
KW - Insulin
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U2 - 10.1016/j.bbi.2014.03.001
DO - 10.1016/j.bbi.2014.03.001
M3 - Article
C2 - 24632224
AN - SCOPUS:84904098523
SN - 0889-1591
VL - 40
SP - 121
EP - 130
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -