Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity
Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity
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DOI：
10.1152/ajpendo.00189.2003
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发表时间：
2004-07-01
影响因子：
5.1
通讯作者：
Kern, PA
中科院分区：
文献类型：
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作者：
Di Gregorio, GB;Hensley, L;Kern, PA
与肥胖相关的胰岛素抵抗可能由诸如白细胞介素 - 6（IL - 6）等脂肪因子引起，已知白细胞介素 - 6在胰岛素抵抗综合征中会升高。先前的一项研究报告称，白细胞介素 - 6基因敲除小鼠（IL - 6（-/-））出现成年发病型肥胖，伴有碳水化合物和脂质代谢紊乱以及瘦素水平升高。由于白细胞介素 - 6与胰岛素抵抗有关，人们可能会预期白细胞介素 - 6（-/-）小鼠对胰岛素更敏感。我们检测了生长中和成年的白细胞介素 - 6（-/-）小鼠的体重，发现它们与野生型（IL - 6（+/+））小鼠相似。在3个月和14个月时进行的双能X射线吸收法分析显示，身体组成没有差异。空腹血胰岛素、血糖以及甘油三酯也没有差异。为了进一步对这些小鼠进行特征分析，我们给11个月大的白细胞介素 - 6（-/-）和白细胞介素 - 6（+/+）小鼠分别喂食高脂肪（HF）或低脂肪饮食14周，然后进行胰岛素耐量试验（ITT）和葡萄糖耐量试验（GTT）。胰岛素耐量试验显示高脂肪饮食的动物存在胰岛素抵抗，但没有因基因型而产生的差异。在葡萄糖耐量试验中，与白细胞介素 - 6（+/+）小鼠相比，白细胞介素 - 6（-/-）小鼠注射后的血糖水平升高了60%，但仅在高脂肪饮食组中出现这种情况。尽管白细胞介素 - 6（-/-）小鼠在高脂肪饮食下体重增加且白色脂肪组织（WAT）增多，但它们体重增加量少于白细胞介素 - 6（+/+）小鼠。与白细胞介素 - 6（+/+）小鼠相比，白细胞介素 - 6（-/-）小鼠白色脂肪组织、肌肉和肝素后血浆中的总脂蛋白脂肪酶活性没有变化。因基因型不同，血浆瘦素或肿瘤坏死因子 - α没有差异。白细胞介素 - 6（-/-）小鼠的血浆脂联素比白细胞介素 - 6（+/+）小鼠高约53%（71.7±14.1微克/毫升），但仅在高脂肪饮食组中如此。因此，这些数据表明，白细胞介素 - 6（-/-）小鼠没有出现肥胖、空腹高血糖或脂质代谢异常，尽管高脂肪饮食的白细胞介素 - 6（-/-）小鼠在葡萄糖耐量试验后血糖升高。
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-alpha due to genotype. Plasma adiponectin was similar to53% higher (71.7+/-14.1 mug/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.