Substance P in the lateral hypothalamic area regulates binge‐like eating behaviors in mice

X Xin-Yue Lv (Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University) Q Qian-Qian Yang (Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University) Y Yue Wang S Si-Ran Wang (Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University) J Jiu-Ye Qiao (Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University) S Shuang Liu (Frontiers Science Center for Transformative Molecules, State Key Laboratory of Polyolefins and Catalysis, School of Chemistry and Chemical Engineering) H Hua-Li Yu (Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University) X Xiao-Xiao He (Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University) X Xiao-Juan Zhu (Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University) Z Zi-Xuan He (Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University)

Abstract

Binge eating disorder (BED) is the most common type of eating disorder; however, the neural circuit mechanisms underlying BED remain elusive. Here, we report that tachykinin-expressing neurons in the lateral hypothalamic area (LH Tac1 neurons) are inhibited during binge-like eating behaviors in mice. We identified LH Tac1 neurons as key mediators of binge-like eating behaviors and reported that the LH Tac1 → lateral periaqueductal gray (LPAG) circuit is critical to the regulation of binge-like eating behaviors. Moreover, Substance P (SP) released by LH Tac1 neurons modulates binge-like eating behaviors by influencing the input of glutamate to LPAG cells, which receive projections from LH Tac1 neurons. In summary, these findings point to the SP as a key node in BED circuits.

Article Details

Volume / Issue Vol. 123, Issue 11
Published March 17, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (10)

X

Xin-Yue Lv

Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University

Q

Qian-Qian Yang

Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University

Y

Yue Wang

S

Si-Ran Wang

Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University

J

Jiu-Ye Qiao

Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University

S

Shuang Liu

Frontiers Science Center for Transformative Molecules, State Key Laboratory of Polyolefins and Catalysis, School of Chemistry and Chemical Engineering

H

Hua-Li Yu

Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University

X

Xiao-Xiao He

Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University

X

Xiao-Juan Zhu

Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University

Z

Zi-Xuan He

Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University