Hedgehog signaling in bone regulates whole-body energy metabolism through a bone–adipose endocrine relay mediated by PTHrP and adiponectin
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AbstractBone 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.
Acceptance Date14/10/2016
All Author(s) ListXu Zhang, Qianni Cheng, Yixiang Wang, Po Sing Leung, Kinglun Kingston Mak
Journal nameCell Death and Differentiation
Volume Number24
PublisherMacmillan Publishers Limited
Place of PublicationUSA
Pages225 - 237
LanguagesEnglish-United States
KeywordsHedgehog signaling, bone, energy metabolism, adiponectin, parathyroid hormone-related protein (PTHrP)

Last updated on 2020-05-07 at 23:53