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

Year: 2022

Type: article

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.

Source: Nature Neuroscience

DOI: 10.1038/s41593-022-01208-0

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

Institutions: University of California San Diego, Virginia Tech

Language: English

Topic: Regulation of Appetite and Obesity

Subfield: Endocrine and Autonomic Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $11,390

Funders: U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences

OpenAlex ID: W4311288198