Subcutaneous fat modulates insulin sensitivity in mice by regulating TNF-α expression in visceral fat
Subcutaneous fat modulates insulin sensitivity in mice by regulating TNF-α expression in visceral fat
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DOI：
10.1055/s-2006-954580
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发表时间：
2006-10-01
影响因子：
2.2
通讯作者：
Saito, Y.
中科院分区：
文献类型：
--
作者：
Ishikawa, K.;Takahashi, K.;Saito, Y.
肥胖者的脂肪分布与患各种代谢紊乱的风险有关，例如葡萄糖不耐症、血脂异常和高血压，这些疾病的组合被称为代谢综合征。本研究的目的是通过使用皮下脂肪切除术并随后进行或不进行脂肪移植的小鼠，研究皮下脂肪在调节胰岛素抵抗中的作用及其对内脏脂肪中 TNF-α 表达的影响。部分皮下脂肪切除术后，与假手术对照小鼠相比，小鼠表现出明显更多的内脏脂肪积累。与对照小鼠的水平相比，在加载葡萄糖和胰岛素后，脂肪切除术分别导致血浆胰岛素升高和血浆葡萄糖水平降低。在脂肪切除小鼠的骨骼肌中，胰岛素诱导的 IRS-1 磷酸化减少。将脂肪垫皮下移植到脂肪切除小鼠体内逆转了上述变化，表明这些动物存在胰岛素抵抗。脂肪切除小鼠的脂肪细胞脂肪储存面积和内脏脂肪中脂肪细胞的TNF-α表达显着高于对照组，而皮下移植脂肪则减少了脂肪储存面积和TNF-α表达。使用特异性抗体全身中和 TNF-α 活性也可改善脂肪切除小鼠的胰岛素抵抗。这些研究结果表明，皮下脂肪可能通过改变脂肪储存和内脏脂肪中脂肪细胞的 TNF-α 表达来调节全身胰岛素敏感性。皮下脂肪和内脏脂肪积累之间的平衡对于代谢综合征中全身胰岛素抵抗的发生可能很重要。
The distribution of fat in obese persons is related to the risk of developing various metabolic disorders, such as glucose intolerance, dyslipidemia and hypertension, and the combination of these conditions is known as the metabolic syndrome. The aim of this study was to investigate the role of subcutaneous fat in regulating insulin resistance and its influence on TNF-alpha expression in visceral fat, by using mice that were subjected to subcutaneous lipectomy with or without subsequent fat transplantation. After partial subcutaneous lipectomy, mice showed significantly greater accumulation of visceral fat compared with sham-operated control mice. Lipectomy led to higher plasma insulin and lower plasma glucose levels after loading with glucose and insulin, respectively, compared with the levels in control mice. Insulin-induced phosphorylation of IRS-1 was decreased in the skeletal muscles of lipectomized mice. Subcutaneous transplantation of fat pads into lipectomized mice reversed the above-mentioned changes indicating insulin resistance in these animals. The fat storage area of adipocytes and TNF-alpha expression by adipocytes in visceral fat were significantly higher in the lipectomized mice than in controls, while subcutaneous transplantation of fat reduced both the fat storage area and TNF-alpha expression. The insulin resistance of lipectomized mice was also ameliorated by systemic neutralization of TNF-alpha activity using a specific antibody. These findings obtained in mice subjected to subcutaneous lipectomy with/without subsequent fat transplantation indicate that subcutaneous fat regulates systemic insulin sensitivity, possibly through altering fat storage and the expression of TNF-alpha by adipocytes in visceral fat. The balance between accumulation of subcutaneous fat and visceral fat may be important with respect to the occurrence of systemic insulin resistance in the metabolic syndrome.