A POMC-originated circuit regulates stress-induced hypophagia,depression, and anhedonia

Authors: QU, NA - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); HE, YANLIN - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); WANG, CHUNMEI - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); XU, PINGWEN - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); YANG, YONGJIE - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); CAI, XING - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); LIU, HESONG - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); YU, KAIFAN - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); PEI, ZHOU - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); HYSENI, LLIRJANA - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); SUN, ZHENG - BAYLOR COLLEGE OF MEDICINE; FUKUDA, MAKOTO - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); LI, YI - HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY; TIAN, QING - HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY; XU, YONG - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)

Submitted to: Molecular Psychiatry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/18/2019
Publication Date: 9/5/2019
Citation: Qu, N., He, Y., Wang, C., Xu, P., Yang, Y., Cai, X., Liu, H., Yu, K., Pei, Z., Hyseni, L., Sun, Z., Fukuda, M., Li, Y., Tian, Q., Xu, Y. 2019. A POMC-originated circuit regulates stress-induced hypophagia, depression, and anhedonia. Molecular Psychiatry. 25:1006-1021. https://doi.org/10.1038/s41380-019-0506-1.
DOI: https://doi.org/10.1038/s41380-019-0506-1

Interpretive Summary: Body weight and eating behavior can be regulated by stress and emotions. However, the brain mechanisms for the regulation of these behaviors remain unclear. Here we discovered a novel neural circuit within the brain that regulate both moods and body weight balance in response to stress. This is important as it may provide a neurobiological basis for the link between obesity and psychiatric disorders.

Technical Abstract: Chronic stress causes dysregulations of mood and energy homeostasis, but the neurocircuitry underlying these alterations remain to be fully elucidated. Here we demonstrate that chronic restraint stress in mice results in hyperactivity of proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus (POMC^ARH neurons) associated with decreased neural activities of dopamine neurons in the ventral tegmental area (DA^VTA neurons). We further revealed that POMC^ARH neurons project to the VTA and provide an inhibitory tone to DA^VTA neurons via both direct and indirect neurotransmissions. Finally, we show that photoinhibition of the POMC^ARH->VTA circuit in mice increases body weight and food intake, and reduces depression-like behaviors and anhedonia in mice exposed to chronic restraint stress. Thus, our results identified a novel neurocircuitry regulating feeding and mood in response to stress.