Oncostatin M is a potential agent for the treatment of obesity and related metabolic disorders: a study in mice

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• 作者：Tadasuke Komori ; Minoru Tanaka ; Hiroto Furuta ; Takashi Akamizu…
• 关键词：Adipose tissue inflammation ; Hepatic steatosis ; High ; fat diet ; Insulin resistance ; Lipid absorption ; Metabolic disorders ; Obesity ; Therapeutic agent
• 刊名：Diabetologia
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：58
• 期：8
• 页码：1868-1876
• 全文大小：2,396 KB
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• 作者单位：Tadasuke Komori (1)
  Minoru Tanaka (2)
  Hiroto Furuta (3)
  Takashi Akamizu (3)
  Atsushi Miyajima (4)
  Yoshihiro Morikawa (1)
  
  1. Department of Anatomy and Neurobiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan
  2. Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
  3. The First Department of Medicine, Wakayama Medical University, Wakayama, Japan
  4. Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Internal Medicine
  Metabolic Diseases
  Human Physiology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0428

文摘

Aims/hypothesis 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/interpretation We showed that OSM is a novel candidate to act as a powerful therapeutic agent for the treatment of obesity-induced metabolic disorders.