title: Cyclosporin A attenuates weight gain and improves glucose tolerance in diet-induced obese mice.
abstract: Inflammation is a main factor responsible for obesity induced insulin resistance and type 2 diabetes. Since immunosuppressant activity is closely related with low level of inflammation, we predict that Cyclosporin A (CsA), an immunosuppressant drug, might have a protective role for combating inflammation-associated disorders such as obesity and type 2 diabetes. To address this issue, obese or lean mice were received CsA via gavage at the dose of 10mg/kg/day for 3 weeks. Our results show that CsA treatment remarkably attenuates food intake and body weight gain in the obese mice. CsA treatment down-regulates expression of gluconeogenic gene including Pepck, G6Pase and Pgc1α, leading to a decrease in blood glucose level and an improvement of glucose tolerance in the obese animals. RT-PCR analysis of genes involved in adipocyte differentiation and lipid metabolism in white adipose tissue reveal that CsA application reduces expression of Pparγ, Fas and Scd 1. The productions of pro-inflammatory cytokines (IL-1β, IL-2, IL-12 and TNFα) and JNK activity were remarkably reduced in the CsA-treated obese animals. These results suggest that CsA treatment might play beneficial effects against obesity and obesity related hyperglycemia.
authors.affiliation: Model Animal Research Center, MOE Key Laboratory of Model Animals for Disease Study, Nanjing University, Nanjing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Jiang
authors.forename: Caiping
authors.initials: C
authors.lastname: Wang
authors.forename: Qingzhou
authors.initials: Q
authors.lastname: Meng
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Kaixuan
authors.initials: K
authors.lastname: Li
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002454:Cell Differentiation / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004435:Eating / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000235:genetics; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation; D007333:Insulin Resistance; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D009765:Obesity / Q000188:drug therapy*; D047495:PPAR gamma / Q000096:biosynthesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects*; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D007376:Interleukin-2; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D018664:Interleukin-12; D016572:Cyclosporine; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; C069767:phosphoenolpyruvate carboxylase kinase; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D005952:Glucose-6-Phosphatase; D005947:Glucose