Language

English

Publication Date

5-13-2026

Journal

Nature Communications

DOI

10.1038/s41467-026-73102-3

PMID

42129178

PMCID

PMC13376941

PubMedCentral® Posted Date

5-13-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Stress and diet are known to synergistically promote risks of obesity but the underlying neural basis remains elusive. Corticotropin-releasing hormone neurons in the paraventricular hypothalamus (PVHCRH) are stress responsive and release both CRH and glutamate. Here we generated a mouse model with gain or loss of release in CRH or glutamate from PVHCRH neurons. While these models showed no changes in body weight when fed chow, they exhibited contrasting effects when fed high-fat high-caloric diets (HFD). Whereas disrupting glutamate release from PVHCRH neurons led to diet-induced obesity (DIO), that of CRH caused no impact. Conversely, augmented CRH release led to DIO while that of glutamate caused no impact. The observed DIO in both cases was associated with an increased drive for HFD, but without obvious changes in behavioral signs of anxiety. Our results suggest PVHCRH neurons as a key mediator for the exerbated DIO induced by maladaptive stress responses.

Keywords

Animals, Obesity, Corticotropin-Releasing Hormone, Paraventricular Hypothalamic Nucleus, Diet, High-Fat, Mice, Neurons, Glutamic Acid, Neurotransmitter Agents, Male, Mice, Inbred C57BL, Body Weight, Neurotransmitters, Obesity

Published Open-Access

yes

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