title: Interleukin-6 regulates the expression of hypothalamic neuropeptides involved in body weight in a gender-dependent way.
abstract: Interleukin (IL)-6 has been involved in the control of body weight and body fat. Nevertheless, the mechanisms underlying these effects are not completely understood because central and peripheral actions of IL-6 are plausible. To gain further insight into the central effects of IL-6, we used transgenic mice expressing the IL-6 gene under the control of the glial fibrillary acidic protein (GFAP) promoter (GFAP-IL-6 mice), therefore with central nervous system-restricted over-expression of IL-6, and we studied the expression of the main neuropeptides responsible for energy homeostasis in specific hypothalamic nuclei. Neuropeptide Y (NPY), agouti-related peptide (AgRP), melanin-concentrating hormone (MCH), prepro-orexin (preproOX) (orexigenic and anabolic neuropeptides), pro-opiomelanocortin (POMC) and corticotrophin-releasing hormone (CRH) (anorexigenic and catabolic peptides) mRNA levels were determined using in situ hybridisation in young (2-4 month-old) and old (10-12 month-old) female and male mice under different feeding conditions: normal diet (control) and high-fat diet (HFD), and 24 h-food deprivation. In GFAP-IL-6 females fed a control diet (GFAP-IL-6-control), we showed a significant decrease in NPY and AgRP mRNA levels at all ages, and a late increase in POMC expression (only significant in older animals). These differences were blunted in HFD mice. By contrast, GFAP-IL-6-control males showed a decrease in CRH mRNA content at early ages (2-4 months), and an increase in older mice (10-12 months). Interestingly, these differences were again blunted in HFD mice. Finally, central IL-6 was not able to counteract the effects of 24 h of fasting on body weight, plasma glucose levels and the mRNA content of the peptides evaluated in the present study. Our results demonstrate that IL-6 may regulate the expression of hypothalamic neuropeptides involved in the control of body weight and body fat acting at the central level in a gender- and age-dependent way.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain. rosa.senaris@usc.es
authors.forename: R M
authors.initials: RM
authors.lastname: Señarís
authors.forename: M L
authors.initials: ML
authors.lastname: Trujillo
authors.forename: B
authors.initials: B
authors.lastname: Navia
authors.forename: G
authors.initials: G
authors.lastname: Comes
authors.forename: B
authors.initials: B
authors.lastname: Ferrer
authors.forename: M
authors.initials: M
authors.lastname: Giralt
authors.forename: J
authors.initials: J
authors.lastname: Hidalgo
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004734:Energy Metabolism; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D007028:Hypothalamic Hormones / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins; D010907:Pituitary Hormones / Q000235:genetics / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics
chemical_list: D054369:Agouti-Related Protein; D001786:Blood Glucose; D007028:Hypothalamic Hormones; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; D011333:Pro-Opiomelanocortin; C019463:melanin-concentrating hormone; D003346:Corticotropin-Releasing Hormone