Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus-brainstem pathway.
Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus-brainstem pathway.
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DOI：
10.1038/s41593-022-01208-0
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发表时间：
2023-01
影响因子：
25
通讯作者：
Lim, Byung Kook
中科院分区：
文献类型：
--
作者：
Shin, Sora;You, In-Jee;Jeong, Minju;Bae, Yeeun;Wang, Xiao-Yun;Cawley, Mikel Leann;Han, Abraham;Lim, Byung Kook
早期生活创伤（ELT）是日后暴饮暴食和肥胖的一个风险因素，但这种关联背后的神经回路尚未得到解决。在这里，我们在小鼠实验中发现，外侧下丘脑（LH）瘦素受体（Lepr）的下调及其对神经活动的影响是导致高脂肪饮食暴露后elt诱导的暴饮暴食和肥胖的关键。我们还发现，在ELT小鼠中，表达lepr的LH （LHLepr）神经元活性的增加编码了持续的暴食样饮食。抑制LHLepr神经元投射到腹外侧导水管周围灰质使ELT小鼠的这些行为特征正常化。此外，表达proenkephalin的腹外侧导水管周围灰色神经元的激活（该神经元接受LHLepr神经元的抑制性输入）可以挽救elt诱导的不良饮食习惯。我们的研究结果确定了介导elt诱导的不适应饮食的电路通路，并可能导致暴饮暴食和肥胖的新治疗靶点的确定。早年创伤是日后暴食和肥胖的风险因素。Shin等人在小鼠中发现了一个下丘脑-脑干回路，该回路是早期创伤诱导的高脂肪饮食暴饮暴食和肥胖倾向特征的基础。
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. Early-life trauma is a risk factor for binge eating and obesity later in life. Shin et al. identify a hypothalamus–brainstem circuit in mice that underlies the early-life trauma-induced binge-like consumption of high-fat diet and obesity-prone characteristics.
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影响因子：
5.3
作者：
Baver, Scott B.;Hope, Kevin;O'Connell, Kristen M. S.
通讯作者：
O'Connell, Kristen M. S.
影响因子：
1.5
作者：
Gaur A;Pal GK;Ananthanarayanan PH;Pal P
通讯作者：
Pal P
影响因子：
4.4
作者：
Grissett, NI;Fitzgibbon, ML
通讯作者：
Fitzgibbon, ML
影响因子：
10.9
作者：
Dallman, Mary F.
通讯作者：
Dallman, Mary F.
DOI：
10.3181/00379727-77-18766
发表时间：
1951-01-01
影响因子：
--
作者：
ANAND, BK;BROBECK, JR
通讯作者：
BROBECK, JR