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

First Author  Zhang F Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  1030
PubMed ID  38310104 Mgi Jnum  J:360282
Mgi Id  MGI:7581426 Doi  10.1038/s41467-024-45436-3
Citation  Zhang F, et al. (2024) Secretin-dependent signals in the ventromedial hypothalamus regulate energy metabolism and bone homeostasis in mice. Nat Commun 15(1):1030
abstractText  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.
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