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유인지In-Jee You

Virginia Tech

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Nat. Neurosci., 2022 Dec 12 | doi: 10.1038/s41593-022-01208-0 Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway

Sora Shin^{# 1 2 3 4}, In-Jee You^{# 5 6}, Minju Jeong ⁷, Yeeun Bae ^{5 6 8}, Xiao-Yun Wang ⁷, Mikel Leann Cawley ^{5 6}, Abraham Han ^{5 6 8}, Byung Kook Lim ⁹

¹Fralin Biomedical Research Institute at VTC, Roanoke, VA, USA.
²FBRI Center for Neurobiology Research, Roanoke, VA, USA.
³Department of Human Nutrition, Foods, and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
⁴Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
⁵Fralin Biomedical Research Institute at VTC, Roanoke, VA, USA.
⁶FBRI Center for Neurobiology Research, Roanoke, VA, USA.
⁷Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
⁸Department of Human Nutrition, Foods, and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
⁹Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
^#Contributed equally.

These authors contributed equally: Sora Shin, In-Jee You.
These authors jointly supervised this work: Sora Shin, Byung Kook Lim.
Corresponding authors: Correspondence to Sora Shin or Byung Kook Lim.

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 (LH^Lepr) neurons encodes sustained binge-like eating in ELT mice. Inhibition of LH^Lepr 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 LH^Lepr 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.

논문정보

형식Research article
게재일2022년 12월 (BRIC 등록일 2022-12-28)
연구진국외 연구진
분야 의약학 > 신경의학

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