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

Biochim Biophys Acta. 2015 May;1852(5):1001-11. doi: 10.1016/j.bbadis.2015.01.017. Epub 2015 Feb 4.


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.

Keywords: Energy expenditure; IL-6; Insulin resistance; Obesity; Weight loss.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Blotting, Western
  • Diet, High-Fat / adverse effects
  • Fatty Liver / genetics*
  • Fatty Liver / therapy
  • Gene Expression
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • Insulin Resistance / genetics
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Lipolysis / genetics
  • Macrophages / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Obese
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Obesity / etiology
  • Obesity / genetics*
  • Obesity / therapy
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Phosphorylation
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Thermogenesis / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Uncoupling Protein 1
  • Weight Gain / genetics*


  • Interleukin-6
  • Ion Channels
  • Mitochondrial Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • STAT3 Transcription Factor
  • Transcription Factors
  • Ucp1 protein, mouse
  • Uncoupling Protein 1