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

Fengwei Zhang, Wei Qiao (), Ji-an Wei, Zhengyi Tao, Congjia Chen, Yefeng Wu, Minghui Lin, Ka Man Carmen Ng, Li Zhang, Kelvin Wai-Kwok Yeung () and Billy Kwok Chong Chow ()
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Fengwei Zhang: the University of Hong Kong
Wei Qiao: the University of Hong Kong
Ji-an Wei: the University of Hong Kong
Zhengyi Tao: the University of Hong Kong
Congjia Chen: the University of Hong Kong
Yefeng Wu: the University of Hong Kong
Minghui Lin: the University of Hong Kong
Ka Man Carmen Ng: the University of Hong Kong
Li Zhang: Jinan University
Kelvin Wai-Kwok Yeung: the University of Hong Kong-Shenzhen Hospital
Billy Kwok Chong Chow: the University of Hong Kong

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-45436-3

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