TY - JOUR
T1 - Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene
T2 - Absence of development of age-related obesity
AU - Di Gregorio, Gina B.
AU - Hensley, Lori
AU - Lu, Tong
AU - Ranganathan, Gouri
AU - Kern, Philip A.
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
KW - Adipose tissue
KW - Interleukin-6
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U2 - 10.1152/ajpendo.00189.2003
DO - 10.1152/ajpendo.00189.2003
M3 - Article
C2 - 15191885
AN - SCOPUS:3042739678
SN - 0193-1849
VL - 287
SP - E182-E187
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 1 50-1
ER -