美国加州大学Byung Kook Lim和弗吉尼亚理工学院Sora Shin研究团队合作取得进展。他们的研究发现早期逆境通过重塑下丘脑-脑干外侧的瘦素反应通路促进类似暴饮暴食的饮食习惯。2022年12月12日，国际学术期刊《自然-神经科学》发表了这一成果。

研究人员在小鼠中发现下丘脑外侧（LH）瘦素受体（麻风病）的下调及其对神经活动的影响，对于暴露在高脂肪饮食时早期创伤（ELT）诱导的暴饮暴食和肥胖至关重要。研究还发现，表达麻风病的LH（LHLepr）神经元活性增加与ELT小鼠的持续暴饮暴食有关。抑制ELT小鼠中LHLepr神经元投射到腹外侧导水管灰质可使这些行为正常化。

此外，激活表达原脑啡肽的腹外侧导水管灰色神经元，挽救了ELT诱导的不良饮食习惯，这些神经元接收了来自LHLepr神经元的抑制性输入。这些研究结果揭示了ELT诱导适应不良饮食的神经回路，这可能有利于发现治疗暴饮暴食和肥胖的新靶点。

据了解，ELT是晚年暴饮暴食和肥胖的危险因素，但尚不清楚这种关联的神经回路。

附：英文原文

Title: Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway

Author: Shin, Sora, You, In-Jee, Jeong, Minju, Bae, Yeeun, Wang, Xiao-Yun, Cawley, Mikel Leann, Han, Abraham, Lim, Byung Kook

Issue&Volume: 2022-12-12

Abstract: Early-life trauma (ELT) is a risk factor for binge eating and obesity later in life, yet the neural circuits that underlie this association have not been addressed. Here, we show in mice that downregulation of the leptin receptor (Lepr) in the lateral hypothalamus (LH) and its effect on neural activity is crucial in causing ELT-induced binge-like eating and obesity upon high-fat diet exposure. We also found that the increased activity of Lepr-expressing LH (LHLepr) neurons encodes sustained binge-like eating in ELT mice. Inhibition of LHLepr neurons projecting to the ventrolateral periaqueductal gray normalizes these behavioral features of ELT mice. Furthermore, activation of proenkephalin-expressing ventrolateral periaqueductal gray neurons, which receive inhibitory inputs from LHLepr neurons, rescues ELT-induced maladaptive eating habits. Our results identify a circuit pathway that mediates ELT-induced maladaptive eating and may lead to the identification of novel therapeutic targets for binge eating and obesity.

DOI: 10.1038/s41593-022-01208-0

Source: https://www.nature.com/articles/s41593-022-01208-0