Hepatocyte Growth Factor Prevented High-Fat Diet-Induced Obesity and Improved Insulin Resistance in Mice.
Hepatocyte Growth Factor Prevented High-Fat Diet-Induced Obesity and Improved Insulin Resistance in Mice.
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DOI：
10.1038/s41598-017-00199-4
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发表时间：
2017-03-09
影响因子：
4.6
通讯作者：
Morishita R
中科院分区：
文献类型：
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作者：
Muratsu J;Iwabayashi M;Sanada F;Taniyama Y;Otsu R;Rakugi H;Morishita R
肥胖及其相关的脂肪组织慢性炎症引发胰岛素抵抗，这与包括高血压和动脉粥样硬化在内的几种病理学有关。以往的研究表明，循环肝细胞生长因子（HGF）水平与肥胖和2型糖尿病有关。然而，其在肥胖和相关病理学中的确切作用尚不清楚。在该实验中，使用小鼠（HGF-Tg小鼠）中心脏特异性过表达的人HGF，其显示出比野生型小鼠高4-5倍的血清HGF水平。虽然用高脂饮食（HFD）喂养14周的野生型小鼠的体重显著增加，伴有胰岛素抵抗，但HGF-Tg小鼠防止体重增加和胰岛素抵抗。与野生型小鼠相比，HGF-Tg小鼠脂肪组织中巨噬细胞的积累和炎症介质水平的升高受到显著抑制。在用HGF中和抗体处理的野生型小鼠中，HFD诱导的肥胖显示出对葡萄糖耐量试验的加剧反应。这些功能获得和功能丧失的研究表明，由HFD诱导的升高的HGF水平对肥胖和胰岛素抵抗具有保护作用。
Obesity and its associated chronic inflammation in adipose tissue initiate insulin resistance, which is related to several pathologies including hypertension and atherosclerosis. Previous reports demonstrated that circulating hepatocyte growth factor (HGF) level was associated with obesity and type 2 diabetes. However, its precise role in obesity and related-pathology is unclear. In this experiment, cardiac-specific over-expression of human HGF in mice (HGF-Tg mice) which showed 4–5 times higher serum HGF levels than wild-type mice were used. While body weight in wild-type mice fed with high fat diet (HFD) for 14 weeks was significantly increased accompanied with insulin resistance, HGF-Tg mice prevented body weight gain and insulin resistance. The accumulation of macrophages and elevated levels of inflammatory mediators in adipose tissue were significantly inhibited in HGF-Tg mice as compared to wild-type mice. The HFD-induced obesity in wild-type mice treated with HGF-neutralizing antibody showed an exacerbated response to the glucose tolerance test. These gain-of-function and loss-of-function studies demonstrated that the elevated HGF level induced by HFD have protective role against obesity and insulin resistance.