Children’s Nutrition Research Center Staff Publications
Publication Date
7-3-2020
Journal
EMBO Reports
DOI
10.15252/embr.201949210
PMID
32462726
PMCID
PMC7332802
PubMedCentral® Posted Date
5-27-2020
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Corticotropin-Releasing Hormone, Hypothalamus, Mice, Neurons, Obesity, Pituitary Hormone-Releasing Hormones, CRH, HFD, obesity, PVH, stress, Metabolism, Neuroscience
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.
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Dietetics and Clinical Nutrition Commons, Endocrinology, Diabetes, and Metabolism Commons, Neurosciences Commons, Nutrition Commons