Volume 35, No 3, Mar 2025

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 35 Issue 3, March 2025: 165-185   |  Open Access

ORIGINAL ARTICLES

Raptin, a sleep-induced hypothalamic hormone, suppresses appetite and obesity

Ling-Qi Xie^1,† , Biao Hu^1,† , Ren-Bin Lu¹ , Ya-Lun Cheng¹ , Xin Chen¹ , Jie Wen¹ , Yao Xiao¹ , Yu-Ze An¹ , Ning Peng¹ , Yu Dai¹ , Genqing Xie² , Qi Guo¹ , Hui Peng^1,* , Xiang-Hang Luo^1,3,4,5,*

¹Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, China
²Department of Endocrinology, The First People’s Hospital of Xiangtan City, Xiangtan, Hunan, China
³National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
⁴Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China
⁵FuRong Laboratory, Changsha, Hunan, China
^†These authors contributed equally: Ling-Qi Xie, Biao Hu
Correspondence: Hui Peng(penghui11083@csu.edu.cn)Xiang-Hang Luo(xianghangluo@sina.com)

Sleep deficiency is associated with obesity, but the mechanisms underlying this connection remain unclear. Here, we identify a sleep-inducible hypothalamic protein hormone in humans and mice that suppresses obesity. This hormone is cleaved from reticulocalbin-2 (RCN2), and we name it Raptin. Raptin release is timed by the circuit from vasopressin-expressing neurons in the suprachiasmatic nucleus to RCN2-positive neurons in the paraventricular nucleus. Raptin levels peak during sleep, which is blunted by sleep deficiency. Raptin binds to glutamate metabotropic receptor 3 (GRM3) in neurons of the hypothalamus and stomach to inhibit appetite and gastric emptying, respectively. Raptin-GRM3 signaling mediates anorexigenic effects via PI3K-AKT signaling. Of note, we verify the connections between deficiencies in the sleeping state, impaired Raptin release, and obesity in patients with sleep deficiency. Moreover, humans carrying an RCN2 nonsense variant present with night eating syndrome and obesity. These data define a unique hormone that suppresses food intake and prevents obesity.

https://doi.org/10.1038/s41422-025-01078-8

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