title: Modulation of Cell-Mediated Immunity to Suppress High Fat Diet-Induced Obesity and Insulin Resistance.
abstract: OBJECTIVE
  To assess the effect of immune modulators, cyclosporin A and fingolimod, on high fat diet-induced obesity and insulin resistance.
  
  
  METHODS
  C57BL/6 mice were fed a high fat diet and injected intraperitoneally with cyclosporine A, fingolimod, or vehicle twice weekly for 15 weeks. Body weight and food intake were manually measured every other day. Glucose tolerance test, insulin sensitivity, and body composition were examined and compared between the control and the immune modulator treated animals. Tissue samples were collected at the end of the experiment and examined for serum biochemistry, histology, and mRNA levels of marker genes for inflammation, and glucose and lipid metabolism in white and brown adipose tissues and in the liver.
  
  
  RESULTS
  Cyclosporine A and fingolimod suppressed high fat diet-induced weight gain, reduced hepatic fat accumulation, and improved insulin sensitivity. The beneficial effects are associated with altered expression of F4/80, Cd68, Il-6, Tnf-α, and Mcp-1 genes, which are involved in macrophage-related chronic inflammation in adipose and hepatic tissues.
  
  
  CONCLUSIONS
  Immune modulation represents an important intervention for obesity and obesity-associated insulin resistance.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, Athens, Georgia, USA.
authors.forename: Linna
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, Athens, Georgia, USA.|Department of Endocrinology, Tongji University School of Medicine, and Shanghai Tenth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Kexiu
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, Athens, Georgia, USA.
authors.forename: Mingming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Tongji University School of Medicine, and Shanghai Tenth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, Athens, Georgia, USA. dliu@uga.edu.
authors.forename: Dexi
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride
keywords: FTY720; cyclosporine A; inflammation; insulin resistance; obesity