Selective and differential roles of PVH<sup>CRH</sup> neurotransmitters in diet-induced obesity in mice

Nature communications
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Zhiying Jiang, Yuhan Cao, Michelle He, Cunjin Su, Runzhou Yang, Maojie Yang, Jing Cai, Hongli Li, Yuanzhong Xu, Shi-Bin Li, Hiroshi Yamaguchi, Luis de Lecea, Benjamin R Arenkiel, Qingchun Tong

Nat Commun. 2026 May 13. doi: 10.1038/s41467-026-73102-3. Online ahead of 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.

PMID:42129178 | DOI:10.1038/s41467-026-73102-3