Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: Absence of development of age-related obesity

Gina B. Di Gregorio, Lori Hensley, Tong Lu, Gouri Ranganathan, Philip A. Kern

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149 Scopus citations


Obesity-related insulin resistance may be caused by adipokines such as IL-6, which is known to be elevated with the insulin resistance syndrome. A previous study reported that IL-6 knockout mice (IL-6-/-) developed maturity onset obesity, with disturbed carbohydrate and lipid metabolism, and increased leptin levels. Because IL-6 is associated with insulin resistance, one might have expected IL-6-/- mice to be more insulin sensitive. We examined body weights of growing and older IL-6-/- mice and found them to be similar to wild-type (IL-6+/+) mice. Dual-energy X-ray absorptiometry analysis at 3 and 14 mo revealed no differences in body composition. There were no differences in fasting blood insulin and glucose or in triglycerides. To further characterize these mice, we fed 11-mo-old IL-6 -/- and IL-6+/+ mice a high- (HF)- or low-fat diet for 14 wk, followed by insulin (ITT) and glucose tolerance tests (GTT). An ITT showed insulin resistance in the HF animals but no difference due to genotype. In the GTT, IL-6-/- mice demonstrated elevated postinjection glucose levels by 60% compared with IL-6+/+ but only in the HF group. Although IL-6-/- mice gained weight and white adipose tissue (WAT) with the HF diet, they gained less weight than the IL-6+/+ mice. Total lipoprotein lipase activity in WAT, muscle, and postheparin plasma was unchanged in the IL-6-/- mice compared with IL-6+/+ mice. There were no differences in plasma leptin or TNF-α due to genotype. Plasma adiponectin was ∼53% higher (71.7 ± 14.1 μg/ml) in IL-6 -/- mice than in IL-6+/+ mice but only in the HF group. Thus these data show that IL-6-/- mice do not demonstrate obesity, fasting hyperglycemia, or abnormal lipid metabolism, although HF IL-6 -/- mice demonstrate elevated glucose after a GTT.

Original languageEnglish
Pages (from-to)E182-E187
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number1 50-1
StatePublished - Jul 2004


  • Adipose tissue
  • Interleukin-6

ASJC Scopus subject areas

  • General Medicine


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