Adipocyte-specific deletion of IL-6 does not attenuate obesity-induced weight gain or glucose intolerance in mice

Am J Physiol Endocrinol Metab. 2019 Oct 1;317(4):E597-E604. doi: 10.1152/ajpendo.00206.2019. Epub 2019 Aug 6.


It has been suggested that interleukin-6 (IL-6) produced by adipocytes in obesity leads to liver insulin resistance, although this hypothesis has never been definitively tested. Accordingly, we did so by generating adipocyte-specific IL-6-deficient (AdipoIL-6-/-) mice and studying them in the context of diet-induced and genetic obesity. Mice carrying two floxed alleles of IL-6 (C57Bl/6J) were crossed with Cre recombinase-overexpressing mice driven by the adiponectin promoter to generate AdipoIL-6-/- mice. AdipoIL-6-/- and floxed littermate controls were fed a standard chow or high-fat diet (HFD) for 16 wk and comprehensively metabolically phenotyped. In addition to a diet-induced obesity model, we also examined the role of adipocyte-derived IL-6 in a genetic model of obesity and insulin resistance by crossing the AdipoIL-6-/- mice with leptin-deficient (ob/ob) mice. As expected, mice on HFD and ob/ob mice displayed marked weight gain and increased fat mass compared with chow-fed and ob/+ (littermate control) animals, respectively. However, deletion of IL-6 from adipocytes in either model had no effect on glucose tolerance or fasting hyperinsulinemia. We concluded that adipocyte-specific IL-6 does not contribute to whole body glucose intolerance in obese mice.

Keywords: IL-6; adiposity; floxed; glucose tolerance; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Adiponectin / biosynthesis
  • Adiponectin / genetics
  • Adiposity / genetics
  • Animals
  • Body Composition / genetics
  • Diet, High-Fat
  • Glucose Intolerance / etiology
  • Glucose Intolerance / genetics*
  • Insulin Resistance / genetics
  • Interleukin-6 / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / pathology
  • Obesity / complications
  • Obesity / genetics*
  • Obesity / metabolism
  • Weight Gain / genetics*


  • Adiponectin
  • Interleukin-6
  • interleukin-6, mouse