title: Interleukin-6 gene transfer reverses body weight gain and fatty liver in obese mice.
abstract: Interleukin-6 (IL-6) is a multifunctional protein and has a major influence on energy metabolism. The current study was designed to assess the therapeutic effect of overexpression of Il-6 gene through gene transfer on high fat diet-induced obese mice. Hydrodynamic delivery of 1 μg pLIVE-IL6 plasmid per mouse into C57BL/6 obese mice resulted in peak level at 10 ng/ml of circulating IL-6 1 day after gene transfer and above 1n g/ml thereafter for a period of 6 weeks. Persistent Il-6 gene expression did not affect food intake but induced a significant reduction in body weight and improved obesity-associated hepatic steatosis. Il-6 gene delivery enhanced thermogenic gene expression and elevated protein levels of phosphorylated STAT3, PGC1α and UCP1 in brown adipose tissue. Il-6 overexpression elevated mRNA levels of lipolysis genes, triggered phosphorylation of STAT3, AMPK, and ACC, and increased expression of genes involved in fatty acid oxidation in skeletal muscle. IL-6 did not affect macrophage infiltration but maintained the M2 macrophage population in adipose tissue. Collectively, these results suggest that overexpression of the Il-6 gene by hydrodynamic gene delivery induces weight loss and alleviates obesity-induced fatty liver and insulin resistance, supporting the notion that gene transfer is a valid approach in managing obesity epidemics.
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, GA 30602, USA.
authors: Yongjie
authors: Y
authors: Ma
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, GA 30602, USA.
authors: Mingming
authors: M
authors: Gao
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, GA 30602, USA.
authors: Hao
authors: H
authors: Sun
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, GA 30602, USA. Electronic address: dliu@uga.edu.
authors: Dexi
authors: D
authors: Liu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000235:genetics* / Q000628:therapy; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D007333:Insulin Resistance / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008066:Lipolysis / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D022722:Thermogenesis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1; D015430:Weight Gain / Q000235:genetics*
chemical_list: D015850:Interleukin-6; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1
keywords: Energy expenditure; IL-6; Insulin resistance; Obesity; Weight loss