Role of muscle IL-6 in gender-specific metabolism in mice.
The aim of the present work was to further explore the physiological roles of muscle-derived IL-6. Adult-floxed and conditional skeletal muscle IL-6 knock out male and female mice were used to study energy expenditure (indirect calorimetry at rest and during treadmill exercise, and body temperature cycle during the light phase) and energy intake (response to fast/refeeding). We also evaluated the responses to leptin and the activity of the insulin signalling pathway in skeletal muscle and liver by phosphorylation of Akt at Ser 473. The stress response was also studied. Results indicate a relevant role of muscle IL-6 in maintaining energy homeostasis, especially in males. Absence of muscle IL-6 in male mice results in lower core body temperature in the light phase, increased respiratory exchange ratio (RER) both at rest and during exercise, increased expression of TCA cycle marked gene, citrate synthase in muscle, reduced fat storage and decreased body weight and food consumption in response to leptin. In females, muscle IL-6 deficiency increases VO2 and CO2 levels similarly. Also in contrast to males, energy expenditure (EE) measured over 48h reveals a significant elevation in female mice with muscle IL-6 deficiency; moreover, they show a modified response to fasting-refeeding and to restraint stress. The present results contribute to the understanding of the role of muscle IL-6 in male and female mouse metabolism, not only during exercise but also in the basal state and in situations where energy balance is altered.
Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
Amalia
http://orcid.org/0000-0001-8661-8570
A
Molinero
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades metabólicas asociadas CIBERDEM, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas/ Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain.
Antonio
A
Fernandez-Perez
Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
Aina
A
Mogas
Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
Mercedes
M
Giralt
Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
Gemma
G
Comes
Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
Olaya
O
Fernandez-Gayol
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades metabólicas asociadas CIBERDEM, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas/ Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain.
Mario
M
Vallejo
Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
Juan
J
Hidalgo
D000818:Animals; D001831:Body Temperature; D004734:Energy Metabolism; D005080:Exercise Test; D005215:Fasting / Q000378:metabolism / Q000502:physiology; D055786:Gene Knockout Techniques; D007328:Insulin / Q000378:metabolism; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000378:metabolism; D012146:Rest; D012694:Serine / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction; D013312:Stress, Physiological / Q000187:drug effects
D007328:Insulin; D015850:Interleukin-6; D012694:Serine; D051057:Proto-Oncogene Proteins c-akt