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Disrupted hypothalamic CRH neuron responsiveness contributes to diet‐induced obesity
Author(s) -
Zhu Canjun,
Xu Yuanzhong,
Jiang Zhiying,
Tian Jin Bin,
Cassidy Ryan M,
Cai ZhaoLin,
Shu Gang,
Xu Yong,
Xue Mingshan,
Arenkiel Benjamin R,
Jiang Qingyan,
Tong Qingchun
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949210
Subject(s) - obesity , hypothalamus , neuron , microbiology and biotechnology , chemistry , biology , endocrinology , medicine , neuroscience
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.