Secretin-dependent signals in the ventromedial hypothalamus regulate energy metabolism and bone homeostasis in mice.

Autor: Zhang F; School of Biological Sciences, the University of Hong Kong, Hong Kong, China., Qiao W; Applied Oral Sciences & Community Dental Care, Faculty of Dentistry, the University of Hong Kong, Hong Kong, China. drqiao@hku.hk.; Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, the University of Hong Kong-Shenzhen Hospital, Shenzhen, China. drqiao@hku.hk., Wei JA; School of Biological Sciences, the University of Hong Kong, Hong Kong, China.; Key Laboratory of CNS Regeneration (Ministry of Education), GHM Institute of CNS Regeneration, Jinan University, Guangzhou, China., Tao Z; School of Biological Sciences, the University of Hong Kong, Hong Kong, China., Chen C; School of Biological Sciences, the University of Hong Kong, Hong Kong, China., Wu Y; Applied Oral Sciences & Community Dental Care, Faculty of Dentistry, the University of Hong Kong, Hong Kong, China., Lin M; School of Biological Sciences, the University of Hong Kong, Hong Kong, China., Ng KMC; School of Biological Sciences, the University of Hong Kong, Hong Kong, China., Zhang L; Key Laboratory of CNS Regeneration (Ministry of Education), GHM Institute of CNS Regeneration, Jinan University, Guangzhou, China.; Neuroscience and Neurorehabilitation Institute, University of Health and Rehabilitation Sciences, Qingdao, China., Yeung KW; Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, the University of Hong Kong-Shenzhen Hospital, Shenzhen, China. wkkyeung@hku.hk.; Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China. wkkyeung@hku.hk., Chow BKC; School of Biological Sciences, the University of Hong Kong, Hong Kong, China. bkcc@hku.hk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 03; Vol. 15 (1), pp. 1030. Date of Electronic Publication: 2024 Feb 03.
DOI: 10.1038/s41467-024-45436-3
Abstrakt: Secretin, though originally discovered as a gut-derived hormone, is recently found to be abundantly expressed in the ventromedial hypothalamus, from which the central neural system controls satiety, energy metabolism, and bone homeostasis. However, the functional significance of secretin in the ventromedial hypothalamus remains unclear. Here we show that the loss of ventromedial hypothalamus-derived secretin leads to osteopenia in male and female mice, which is primarily induced by diminished cAMP response element-binding protein phosphorylation and upregulation in peripheral sympathetic activity. Moreover, the ventromedial hypothalamus-secretin inhibition also contributes to hyperphagia, dysregulated lipogenesis, and impaired thermogenesis, resulting in obesity in male and female mice. Conversely, overexpression of secretin in the ventromedial hypothalamus promotes bone mass accrual in mice of both sexes. Collectively, our findings identify an unappreciated secretin signaling in the central neural system for the regulation of energy and bone metabolism, which may serve as a new target for the clinical management of obesity and osteoporosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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