title: Hydrodynamic delivery of adiponectin and adiponectin receptor 2 gene blocks high-fat diet-induced obesity and insulin resistance.
abstract: Adiponectin and its receptors are inversely related to the degree of obesity and have been identified as potential therapeutic targets for the treatment of obesity. In this study, we evaluated the effect of hydrodynamic delivery of adiponectin and/or its receptor 2 (adipoR2) genes on controlling the development of obesity and insulin resistance in AKR/J mice fed a high-fat diet. An increase in adiponectin and adipoR2 gene expression by hydrodynamic gene delivery prevented diet-induced weight gain, reduced fat accumulation in liver and adipose tissue, and improved insulin sensitivity. Beneficial effects were seen with reduced gluconeogenesis in the liver and lipogenesis in the liver, white adipose tissue and skeletal muscle. Real-time PCR analysis demonstrated overexpression of adiponectin and adipoR2 significantly suppressed transcription of phosphoenolpyruvate carboxykinase (pepck), glucose-6-phosphatase (g6pase), stearoyl CoA desaturase 1 (scd-1) and fatty acid synthase (fas) gene. Inhibition effects were mediated by activating the AMP-activated protein kinase (AMPK). These results prove that elevation of adiponectin and/or adipoR2 expression via gene transfer is an effective approach in managing obesity epidemics.
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
authors: Y
authors: Y
authors: Ma
authors: D
authors: D
authors: Liu
mesh_terms: D052242:Adiponectin / Q000008:administration & dosage / Q000235:genetics*; D000818:Animals; D059305:Diet, High-Fat; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D057446:Hydrodynamics; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D051379:Mice; D009765:Obesity / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000037:antagonists & inhibitors / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000008:administration & dosage / Q000235:genetics*; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C475420:ADIPOR2 protein, human; D052242:Adiponectin; D007328:Insulin; D054419:Receptors, Adiponectin; D013230:Stearoyl-CoA Desaturase; D064429:Fatty Acid Synthases; D005952:Glucose-6-Phosphatase; D019764:Phosphoenolpyruvate Carboxykinase (ATP)