Loss of Adipose Growth Hormone Receptor in Mice Enhances Local Fatty Acid Trapping and Impairs Brown Adipose Tissue Thermogenesis
Loss of Adipose Growth Hormone Receptor in Mice Enhances Local Fatty Acid Trapping and Impairs Brown Adipose Tissue Thermogenesis
复制标题
小鼠脂肪生长激素受体的丧失会增强局部脂肪酸捕获并损害棕色脂肪组织的生热作用
DOI：
10.1016/j.isci.2019.05.020
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发表时间：
2019-06-28
期刊：
影响因子：
5.8
通讯作者：
Wu, Yingjie
中科院分区：
文献类型：
--
作者：
Ran, Liyuan;Wang, Xiaoshuang;Wu, Yingjie
生长激素（GH）与其受体（生长激素受体[GHR]）结合，发挥其对生长和代谢的多效性作用。GH/GHR作用的破坏不仅使生长失败，而且还涉及许多代谢紊乱，如具有全局或组织特异性Ghr缺乏的小鼠模型和临床观察所示。本研究构建了脂肪特异性Ghr基因敲除小鼠模型Ad-GHRKO，并研究了其在高脂饮食和寒冷应激下的代谢适应性。我们发现，脂肪Ghr的破坏加速饮食性肥胖，但通过游离脂肪酸捕获保护肝脏免受异位肥胖。产热的棕色脂肪组织燃烧和冷诱导的白色脂肪组织布朗宁在没有脂肪Ghr的情况下减慢，但在长时间的冷习服后恢复。我们的结论是，以皮下脂肪过度积累和较低的紧急耐冷性为代价，下调脂肪GHR信号传导模拟了健康的肥胖情况，这对HFD具有代谢优势。
Growth hormone (GH) binds to its receptor (growth hormone receptor [GHR]) to exert its pleiotropic effects on growth and metabolism. Disrupted GH/GHR actions not only fail growth but also are involved in many metabolic disorders, as shown in murine models with global or tissue-specific Ghr deficiency and clinical observations. Here we constructed an adipose-specific Ghr knockout mouse model Ad-GHRKO and studied the metabolic adaptability of the mice when stressed by high-fat diet (HFD) or cold. We found that disruption of adipose Ghr accelerated dietary obesity but protected the liver from ectopic adiposity through free fatty add trapping. The heat-producing brown adipose tissue burning and white adipose tissue browning induced by cold were slowed in the absence of adipose Ghr but were recovered after prolonged cold acclimation. We conclude that at the expense of excessive subcutaneous fat accumulation and lower emergent cold tolerance, down-tuning adipose GHR signaling emulates a healthy obesity situation which has metabolic advantages against HFD.