Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake

• 成果类型: Article
• 署名作者: Tan, Han L.; Yin, Luping; Tan, Yuqi; Ivanov, Jessica; Plucinska, Kaja; Ilanges, Anoj; Herb, Brian R.; Wang, Putianqi; Kosse, Christin; Cohen, Paul; Lin, Dayu; Friedman, Jeffrey M.
• 署名单位: Rockefeller University; Howard Hughes Medical Institute; NYU Langone Medical Center; New York University; Stanford University; Rockefeller University; University System of Maryland; University of Maryland Baltimore
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4784
• DOI: 10.1038/s41586-024-08108-2
• 发表日期: 2024-12-05
• 页码: 198-+
• 关键词: adult mice; pomc neurons; basonuclin 2; expression; agrp; sensitivity; atlas; gene

摘要

Leptin is an adipose tissue hormone that maintains homeostatic control of adipose tissue mass by regulating the activity of specific neural populations controlling appetite and metabolism(1). Leptin regulates food intake by inhibiting orexigenic agouti-related protein (AGRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons(2). However, whereas AGRP neurons regulate food intake on a rapid time scale, acute activation of POMC neurons has only a minimal effect(3-5). This has raised the possibility that there is a heretofore unidentified leptin-regulated neural population that rapidly suppresses appetite. Here we report the discovery of a new population of leptin-target neurons expressing basonuclin 2 (Bnc2) in the arcuate nucleus that acutely suppress appetite by directly inhibiting AGRP neurons. Opposite to the effect of AGRP activation, BNC2 neuronal activation elicited a place preference indicative of positive valence in hungry but not fed mice. The activity of BNC2 neurons is modulated by leptin, sensory food cues and nutritional status. Finally, deleting leptin receptors in BNC2 neurons caused marked hyperphagia and obesity, similar to that observed in a leptin receptor knockout in AGRP neurons. These data indicate that BNC2-expressing neurons are a key component of the neural circuit that maintains energy balance, thus filling an important gap in our understanding of the regulation of food intake and leptin action.