Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice

Acta Physiol (Oxf). 2014 Aug;211(4):585-96. doi: 10.1111/apha.12328. Epub 2014 Jul 1.


Aim: Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, but because many types of cells can synthesize and respond to IL-6 considerable uncertainty still exists about the mechanisms underlying IL-6 effects. Therefore, the aim of this study was to analyse the effects of tissue-specific deletion of IL-6 using a fatty acid binding protein (aP2) promoter-Cre inducible system (aP2-Cre-ERT2).

Methods: Tissue-specific IL-6 KO mice (aP2-IL-6 KO mice) were produced upon tamoxifen administration and were fed a high-fat diet (HFD, 58.4% kcal from fat) or a control diet (18%) for 14 weeks.

Results: aP2-IL-6 KO female mice on a HFD gained less weight and adiposity than littermate wild-type mice, but these effects were not observed in males. Hypothalamic factors such as NPY and AgRP showed a pattern of expression consistent with this sex-specific phenotype. PGC-1α expression was increased in several tissues in aP2-IL-6 KO female mice, which is compatible with increased energy expenditure. Serum leptin, insulin, glucose, cholesterol and triglycerides levels were increased by HFD, and in females IL-6 deficiency reversed this effect in the case of insulin and cholesterol. HFD induced impaired responses to insulin and glucose tolerance tests, but no significant differences between genotypes were observed.

Conclusion: The present results demonstrate that deletion of IL-6 driven by aP2-Cre regulates body weight, body fat and metabolism in a sex-specific fashion.

Keywords: aP2-Cre-induced IL-6 deficiency; body weight; high-fat diet; hypothalamic factors; insulin signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / physiology*
  • Animals
  • Diet, High-Fat / adverse effects*
  • Fatty Acid-Binding Proteins / metabolism*
  • Female
  • In Situ Hybridization
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Real-Time Polymerase Chain Reaction
  • Weight Gain / physiology*


  • Fabp4 protein, mouse
  • Fatty Acid-Binding Proteins
  • Interleukin-6
  • interleukin-6, mouse