Muscle-specific interleukin-6 deletion influences body weight and body fat in a sex-dependent manner

Beatriz Ferrer, Belén Navia, Mercedes Giralt, Gemma Comes, Javier Carrasco, Amalia Molinero, Albert Quintana, Rosa M. Señarís, Juan Hidalgo

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)121-130
Number of pages10
JournalBrain, Behavior, and Immunity
StatePublished - Aug 2014
Externally publishedYes


  • Body weight
  • High-fat diet
  • Hypothalamic factors
  • IL-6
  • Insulin

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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