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Publication : Interleukin-6 gene transfer reverses body weight gain and fatty liver in obese mice.

First Author  Ma Y Year  2015
Journal  Biochim Biophys Acta Volume  1852
Issue  5 Pages  1001-11
PubMed ID  25660446 Mgi Jnum  J:234581
Mgi Id  MGI:5790289 Doi  10.1016/j.bbadis.2015.01.017
Citation  Ma Y, et al. (2015) Interleukin-6 gene transfer reverses body weight gain and fatty liver in obese mice. Biochim Biophys Acta 1852(5):1001-11
abstractText  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 mug 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, PGC1alpha 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.
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