Spinophilin-deficient Mice are Protected from Diet-induced Obesity and Insulin Resistance.
Spinophilin-deficient Mice are Protected from Diet-induced Obesity and Insulin Resistance.
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DOI：
10.1152/ajpendo.00114.2020
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发表时间：
2020-06
期刊：
影响因子：
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通讯作者：
Yong Zhang;Lili Song;Huansheng Dong;Do-sung Kim;Zhen Sun;H. Boger;Qin Wang;Hongjun Wang
中科院分区：
文献类型：
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作者：
Yong Zhang;Lili Song;Huansheng Dong;Do-sung Kim;Zhen Sun;H. Boger;Qin Wang;Hongjun Wang
白色脂肪组织(WAT)的褐化已被证明可以减少肥胖和肥胖相关的并发症，这表明促进WAT褐化的因素可能在开发治疗肥胖症的策略方面有应用。在这里，我们表明，去除亲刺蛋白(SPL)，一种无处不在的表达，多结构域支架蛋白，增加新陈代谢，改善能量平衡。雄性和雌性SPL基因敲除(KO)和野生型(WT)产仔对照分别饲喂普通饲料或高脂饲料(HFD)。测量并比较体重、肝脏脂肪变性、血糖和胰岛素耐量、体力活动和脂肪组织中褐变基因的表达。饲喂Chow饲料的雄性SPL基因敲除(KO)小鼠明显比野生型(WT)小鼠更瘦，体重更轻，表现出更好的葡萄糖耐量和胰岛素敏感性。当喂食高脂饮食(HFD)时，SPL KO小鼠免受体脂增加、体重增加、肝脏脂肪变性、高胰岛素血症和胰岛素抵抗的影响。与WT对照组相比，SPL KO小鼠的体力活动明显增加。此外，棕色脂肪细胞标记物UCP-1和线粒体活性标记物CD137和c-IDEA在SPL KO小鼠内脏水(VWAT)中的表达显著增加，这表明SPL基因敲除至少部分地通过促进vWAT中白色脂肪细胞的褐化来保护小鼠免受HFD诱导的肥胖及其代谢并发症的影响。我们的数据表明，SPL在调节葡萄糖稳态、肥胖和脂肪细胞褐变方面起着关键作用。这些结果表明，SPL可能是治疗肥胖和糖尿病的药物靶点。
Browning of white adipose tissue (WAT) has been shown to reduce obesity and obesity-related complications suggesting that factors that promote WAT browning may have applications in the development of therapeutic strategies for treating obesity. Here, we show that ablation of spinophilin (SPL), a ubiquitously expressed, multidomain scaffolding protein, increases metabolism and improves energy balance. Male and female SPL knockout (KO) and wild type (WT) littermate controls were fed a Chow diet or a high fat diet (HFD). Body weight, hepatic steatosis, glucose and insulin tolerance, physical activity and expression of browning genes in adipose tissues were measured and compared. Male SPL knockout (KO) mice fed a Chow diet were significantly leaner, had lower body weights, and exhibited better glucose tolerance and insulin sensitivity than wild type (WT) littermate controls. When fed a high fat diet (HFD), spl KO mice were protected from increased body fat, weight gain, hepatic steatosis, hyperinsulinemia, and insulin resistance. Physical activity of spl KO mice was markedly increased compared to WT controls. Furthermore, expression of the brown adipocyte marker, UCP-1, and the mitochondrial activity markers, cd137 and c-idea, were significantly increased in visceral WAT (vWAT) of spl KO mice, suggesting that SPL knockout protected the mice from HFD-induced obesity and its metabolic complications, at least in part, by promoting the browning of white adipocytes in vWAT. Our data identify a critical role of SPL in regulating glucose homeostasis, obesity, and adipocyte browning. These results suggest SPL may serve as a drug target for obesity and diabetes.