美国洛克菲勒大学Jeffrey M. Friedman团队近期取得重要工作进展，他们研究提出，瘦素激活的下丘脑BNC2神经元严重抑制食物摄入。相关研究成果2024年10月30日在线发表于《自然》杂志上。

据介绍，瘦素是一种由脂肪组织分泌的激素，通过调节控制食欲和代谢的特定神经元群体的活动，来维持脂肪组织质量的稳态控制。瘦素通过抑制促食欲的丝氨酸蛋白酪氨酸激酶相关蛋白（AGRP）神经元，并激活厌食的促黑皮质素原（POMC）神经元来调节食物摄入。

然而，尽管AGRP神经元能够在短时间内快速调节食物摄入，POMC神经元的急性激活对食物摄入的影响却很小。这引发了一个可能性，即可能存在一种尚未发现的由瘦素调节的神经元群体，可快速抑制食欲。

研究人员报道了一个新的瘦素靶向神经元群体的发现，这些神经元位于弓状核中，表达Bnc2，通过直接抑制AGRP神经元来急性抑制食欲。与AGRP激活的作用相反，BNC2神经元的激活在饥饿小鼠（而非已进食的小鼠）中引发了指示正价效应的场所偏好。

BNC2神经元的活动受瘦素、食物的感官信号和营养状况的调节。最后，删除BNC2神经元中的瘦素受体导致显著的暴食和肥胖，这与在AGRP神经元中敲除瘦素受体所观察到的情况相似。

总之，这一研究表明，表达BNC2的神经元是维持能量平衡的神经回路中的关键组成部分，填补了人们对食物摄入和瘦素作用调节理解中的重要空白。

附：英文原文

Title: Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake

Author: 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.

Issue&Volume: 2024-10-30

Abstract: 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 metabolism1. Leptin regulates food intake by inhibiting orexigenic agouti-related protein (AGRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons2. However, whereas AGRP neurons regulate food intake on a rapid time scale, acute activation of POMC neurons has only a minimal effect3,4,5. 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.

DOI: 10.1038/s41586-024-08108-2

Source: https://www.nature.com/articles/s41586-024-08108-2