武汉云克隆科技股份有限公司

Abstract: Bone plays a role in energy metabolism, but the interplay between bone and other organs in this process is not completely understood. Here, we show that upregulated Hh signaling in bones results in increased whole-body energy expenditure, white adipose tissue (WAT) browning, hypoglycemia and skeletal muscle atrophy. We found that Hh signaling induces PTHrP secretion from bones and causes WAT browning. Injection of PTHrP-neutralizing antibody attenuates WAT browning and improves the circulating blood glucose level while high-fat diet treatment only rescues hypoglycemia. Furthermore, bone-derived PTHrP stimulates adiponectin secretion in WAT and results in systemic increase of fatty acid oxidation and glucose uptake. Mechanistically, PTHrP activates both PKA/cAMP and Akt/Foxo pathways for Ucp1 expression in WAT. PTHrP couples adiponectin actions to activate the AMPK pathway in the skeletal muscles and liver, respectively, for fatty acid oxidation. Our findings establish a new bone-adipose hormonal relay that regulates whole-body energy metabolism.

摘要：骨在能量代谢中起作用，但在这个过程中骨和其他器官之间的相互作用尚未完全了解。在这里，我们显示骨骼中上调的Hh信号导致全身能量消耗增加，白色脂肪组织（WAT）褐变，低血糖和骨骼肌萎缩。我们发现Hh信号传导诱导PTHrP从骨骼分泌并引起WAT褐变。注射PTHrP中和抗体可减轻WAT褐变并改善循环血糖水平，而高脂饮食治疗仅可挽救低血糖。此外，骨衍生的PTHrP刺激WAT中的脂联素分泌并导致脂肪酸氧化和葡萄糖摄取的系统性增加。机械地，PTHrP激活WAT中Ucp1表达的PKA / cAMP和Akt / Foxo途径。 PTHrP结合脂联素作用，分别激活骨骼肌和肝脏中的AMPK通路，进行脂肪酸氧化。我们的研究结果建立了一种新的调节全身能量代谢的骨 - 脂肪激素接力。

使用试剂原文信息：ELISA Kit for Parathyroid Hormone Related Protein (PTHrP) (SEA819Mu) and recombinant PTHrP (RPA819Mu01) were purchased from Wuhan USCN Business Co., Ltd (Wuhan, China).