Induction of adipose and hepatic SWELL1 expression is required for maintaining systemic insulin-sensitivity in obesity.
Induction of adipose and hepatic SWELL1 expression is required for maintaining systemic insulin-sensitivity in obesity.
复制标题
诱导脂肪和肝脏 SWELL1 表达是维持肥胖患者全身胰岛素敏感性所必需的。
DOI：
10.1080/19336950.2017.1373225
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Sah,Rajan
中科院分区：
文献类型：
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作者：
Xie,Litao;Zhang,Yanhui;Gunasekar,SusheelK;Mishra,Anil;Cao,Lei;Sah,Rajan
肥胖与胰岛素敏感性丧失和全身性血糖异常有关，从而导致2型糖尿病，然而这种关联的分子机制尚不清楚。通过脂肪细胞膜片钳研究，我们最近发现脂肪细胞中的体积调节阴离子电流（VRAC）需要SWELL1，并且SWELL1介导的VRAC可以被脂肪细胞的机械和病理生理扩张激活。我们还证明脂肪细胞SWELL1是维持胰岛素信号和葡萄糖稳态所必需的，特别是在肥胖的情况下。在肥胖的情况下，皮下脂肪、内脏脂肪和肝脏诱导了SWELL1蛋白的表达。在高脂肪饮食中长大的小鼠中，脂肪和肝脏中AAV/rec2-shRNA介导的SWELL1的长期敲低与体重增加、肥胖增加和胰岛素抵抗加剧有关。这些数据进一步支持了这样一种观点，即在营养过度的情况下，SWELL1诱导发生在胰岛素敏感组织（肝脏和脂肪）中，并通过支持胰岛素敏感性的增强来改善全身性血糖。
Obesity is associated with a loss of insulin-sensitivity and systemic dysglycemia, resulting in Type 2 diabetes, however the molecular mechanisms underlying this association are unclear. Through adipocyte patch-clamp studies, we recently showed that SWELL1 is required for the Volume-Regulated Anion Current (VRAC) in adipocytes and that SWELL1-mediated VRAC is activated by both mechanical and pathophysiological adipocyte expansion. We also demonstrated that adipocyte SWELL1 is required for maintaining insulin signaling and glucose homeostasis, particularly in the setting of obesity. Here we show that SWELL1 protein expression is induced in subcutaneous fat, visceral fat and liver in the setting of obesity. Long- term AAV/rec2-shRNA mediated SWELL1 knock-down in both fat and liver are associated with increased weight gain, increased adiposity and exacerbated insulin resistance in mice raised on a high-fat diet. These data further support the notion that SWELL1 induction occurs in insulin- sensitive tissues (liver and adipose) in the setting of over-nutrition and contributes to improved systemic glycemia by supporting enhanced insulin-sensitivity.