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Title: Disrupted hypothalamic CRH neuron responsiveness contributes to diet-induced obesity

Author
item ZHU, CANJUN - University Of Texas Health Science Center
item XU, YUANGZHONG - University Of Texas Health Science Center
item JIANG, ZHIYING - University Of Texas Health Science Center
item TIAN, JIN BIN - University Of Texas Health Science Center
item CASSIDY, RYAN - University Of Texas Health Science Center
item CAI, ZHAO-LIN - Baylor College Of Medicine
item SHU, GANG - South China Agricultural University
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item XUE, MINGSHAN - Baylor College Of Medicine
item ARENKIEL, BENJIAMIN - Baylor College Of Medicine
item JIANG, QINGYAN - South China Agricultural University
item TONG, QINGCHUN - University Of Texas Health Science Center

Submitted to: EMBO Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/28/2020
Publication Date: 7/27/2020
Citation: Zhu, C., Xu, Y., Jiang, Z., Tian, J., Cassidy, R.M., Cai, Z., Shu, G., Xu, Y., Xue, M., Arenkiel, B., Jiang, Q., Tong, Q. 2020. Disrupted hypothalamic CRH neuron responsiveness contributes to diet-induced obesity. EMBO Reports. 21:e49210. https://doi.org/10.15252/embr.201949210.
DOI: https://doi.org/10.15252/embr.201949210

Interpretive Summary: Obesity is a serious health issue to our society but the mechanisms for obesity development is still not clear. The current obesity epidemic mainly results from high-fat high-caloric diet feeding and may also be contributed by chronic stress; however, the neural basis underlying stress-related diet-induced obesity remains unknown. Here we discovered normal responses of a small group of cells within the brain responds to stress. This is important to prevent development of obesity, which may provide the neurobiological basis for the link between eating and stress-related disorders.

Technical Abstract: The current obesity epidemic mainly results from high-fat high-caloric diet (HFD) feeding and may also be contributed by chronic stress; however, the neural basis underlying stress-related diet-induced obesity remains unknown. Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamus (PVH), a known body weight-regulating region, represent one key group of stress-responsive neurons. Here, we found that HFD feeding blunted PVH CRH neuron response to nutritional challenges as well as stress stimuli and dexamethesone, which normally produce rapid activation and inhibition on these neurons, respectively. We generated mouse models with the activity of these neurons clamped at high or low levels, both of which showed HFD-mimicking, blunted PVH CRH neuron responsiveness. Strikingly, both models developed rapid HFD-induced obesity, associated with HFD-mimicking, reduced diurnal rhythmicity in feeding and energy expenditure. Thus, blunted responsiveness of PVH CRH neurons, but not their absolute activity levels, underlies HFD-induced obesity and may also contribute to stress-induced obesity.