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

Lv, Xin-Yue; Yang, Qian-Qian; Wang, Yue; Wang, Si-Ran; Qiao, Jiu-Ye; Liu, Shuang; Yu, Hua-Li; He, Xiao-Xiao et al. · Proc Natl Acad Sci U S A · 2026

basic_science · Level V

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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<sup>Tac1</sup> neurons) are inhibited during binge-like eating behaviors in mice. We identified LH<sup>Tac1</sup> neurons as key mediators of binge-like eating behaviors and reported that the LH<sup>Tac1</sup>→ lateral periaqueductal gray (LPAG) circuit is critical to the regulation of binge-like eating behaviors. Moreover, Substance P (SP) released by LH<sup>Tac1</sup> neurons modulates binge-like eating behaviors by influencing the input of glutamate to LPAG cells, which receive projections from LH<sup>Tac1</sup> neurons. In summary, these findings point to the SP as a key node in BED circuits.

Medical subject headings