Authors
Pedro A Perez, Chung-Chih Liu, Alessandra Ferrari, Nicole K Littlejohn, John Paul Kennelly, Emma Marie Robinson, Vân T B Nguyen-Tran, Jon Athanacio, Sean B Joesph, Zaid Amso, Peter Tontonoz, Supriya Srinivasan
Published in
eLife. Volume 15. Oct 05, 2026. Epub Oct 05, 2026.
Abstract
Neuropeptidergic control of lipid metabolism is conserved and increasingly implicated in metabolic diseases, but receptor-level mechanisms remain unclear. Here, we identify the neurokinin-2 receptor (NK2R) as a central node linking tachykinin signals to intestinal lipid mobilization, epithelial composition, and mucosal inflammation. Across complementary genetic and pharmacological perturbations, modulation of NK2R drives bidirectional effects. Loss or blockade of NK2R increases postprandial triglyceridemia and expands intestinal lipid stores, whereas agonism suppresses chylomicron output, reduces adiposity, and improves glycemia in diet-induced obesity. Transcriptomic and cellular analyses indicate coordinated upregulation of lipid-metabolic programs with a concomitant dampening of immune pathways in the absence of NK2R, accompanied by sex-specific remodeling of secretory lineages and male-biased protection from colitis. NK2R signaling also shaped the fecal microbiota in a genotype- and diet-dependent manner, highlighting crosstalk among neuropeptide signaling, epithelial physiology, and host-microbe interactions. These findings position NK2R as a molecular switch for intestinal lipid handling and mucosal inflammation and suggest that NK2R-targeted agonists or antagonists could be deployed as context- and sex-dependent therapeutic strategies for metabolic disease and inflammatory bowel disease.
PMID:
42831287
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 11
- Comments 0