title: Oncostatin M is a potential agent for the treatment of obesity and related metabolic disorders: a study in mice.
abstract: OBJECTIVE
  Obesity and insulin resistance are closely associated with adipose tissue dysfunction caused by the abnormal recruitment of inflammatory cells, including macrophages. Oncostatin M (OSM), a member of the IL-6 family of cytokines, plays important roles in a variety of biological functions including the regulation of inflammatory responses. In previous reports, we have demonstrated that mice deficient in the OSM receptor β subunit show obesity, adipose tissue inflammation, insulin resistance and hepatic steatosis, all of which are exacerbated by feeding the mice a high-fat diet. These results prompted us to test the therapeutic effects of OSM on obesity-induced metabolic disorders using mouse models of obesity.
  
  
  METHODS
  In diet-induced obese and ob/ob mice, metabolic variables were assessed physiologically, histologically and biochemically after the intraperitoneal injection of recombinant mouse OSM twice a day for 1 week.
  
  
  RESULTS
  Treatment with OSM improved obesity, adipose tissue inflammation, insulin resistance and hepatic steatosis in both mouse models. Although OSM reduced food intake, such therapeutic effects of OSM were observed even under pair-feeding conditions. Functionally, OSM directly changed the phenotype of adipose tissue macrophages from M1 type (inflammatory) to M2 type (anti-inflammatory). In the liver, OSM suppressed the expression of genes related to fatty acid synthesis and increased the expression of genes related to fatty acid oxidation. Furthermore, OSM decreased lipid absorption and increased the expression of active glucagon-like peptide-1 in the intestine.
  
  
  CONCLUSIONS
  We showed that OSM is a novel candidate to act as a powerful therapeutic agent for the treatment of obesity-induced metabolic disorders.
authors.affiliation: Department of Anatomy and Neurobiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan.
authors.forename: Tadasuke
authors.initials: T
authors.lastname: Komori
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hiroto
authors.initials: H
authors.lastname: Furuta
authors.forename: Takashi
authors.initials: T
authors.lastname: Akamizu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Morikawa
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D053683:Oncostatin M / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D053683:Oncostatin M