Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions.
Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions.
复制标题
将有害的内脏脂肪转化为有益的能量燃烧可改善代谢功能障碍
DOI：
10.1172/jci.insight.89044
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发表时间：
2017-02-23
期刊：
影响因子：
8
通讯作者：
Cao Y
中科院分区：
文献类型：
--
作者：
Yang X;Sui W;Zhang M;Dong M;Lim S;Seki T;Guo Z;Fischer C;Lu H;Zhang C;Yang J;Zhang M;Wang Y;Cao C;Gao Y;Zhao X;Sun M;Sun Y;Zhuang R;Samani NJ;Zhang Y;Cao Y
内脏脂肪被认为是真正有害的白色脂肪组织 (WAT)，与代谢紊乱、心血管疾病和癌症的发展相关。在这里，我们提出了一个新概念，将有害的内脏脂肪转化为有益的能量消耗库，这有利于改善肥胖小鼠的代谢功能障碍。我们发现，尽管食物摄入量增加，但内脏脂肪的低温依赖性褐变导致脂肪重量、总体重和体重指数下降。在高脂肪饮食喂养的小鼠中，低温暴露改善了内脏脂肪的褐变、通过非颤抖产热作用的整体代谢、胰岛素敏感性和肝脂肪变性。全基因组表达谱显示 WAT 褐变相关基因（包括 Cidea 和 Dio2）上调。相反，Prdm16 在健康小鼠中没有变化，或者在肥胖小鼠中下调。手术切除内脏脂肪和基因敲低附睾脂肪中的 UCP1 在很大程度上消除了低温增加的整体生热作用，并导致大多数小鼠死亡。因此，内脏脂肪的褐变可能是一种补偿性加热机制，可以为治疗内脏脂肪相关的肥胖和糖尿病提供一种新的治疗策略。
Visceral fat is considered the genuine and harmful white adipose tissue (WAT) that is associated to development of metabolic disorders, cardiovascular disease, and cancer. Here, we present a new concept to turn the harmful visceral fat into a beneficial energy consumption depot, which is beneficial for improvement of metabolic dysfunctions in obese mice. We show that low temperature–dependent browning of visceral fat caused decreased adipose weight, total body weight, and body mass index, despite increased food intake. In high-fat diet–fed mice, low temperature exposure improved browning of visceral fat, global metabolism via nonshivering thermogenesis, insulin sensitivity, and hepatic steatosis. Genome-wide expression profiling showed upregulation of WAT browning–related genes including Cidea and Dio2. Conversely, Prdm16 was unchanged in healthy mice or was downregulated in obese mice. Surgical removal of visceral fat and genetic knockdown of UCP1 in epididymal fat largely ablated low temperature–increased global thermogenesis and resulted in the death of most mice. Thus, browning of visceral fat may be a compensatory heating mechanism that could provide a novel therapeutic strategy for treating visceral fat–associated obesity and diabetes.