NK2R signaling governs intestinal lipid mobilization and mucosal inflammation.

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 p

SUBMITTER: Perez PA 

PROVIDER: S-EPMC12667774 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature