NK2R signaling governs intestinal lipid mobilization and mucosal inflammation

Neuropeptidergic control of lipid metabolism is increasingly understood to play a role in metabolic diseases, but the specific receptor-level mechanisms have been elusive. This study reveals the neurokinin-2 receptor (NK2R) as a crucial link between tachykinin signals and intestinal lipid mobilization, epithelial composition, and mucosal inflammation.

The researchers found that altering NK2R levels leads to both increasing post-meal triglyceride levels and expanding fat tissue, as well as suppressing chylomicron release, reducing adiposity, and improving blood sugar control in obese individuals. Genomic and cellular studies showed that without NK2R, there is an increase in lipid metabolism and a decrease in immune responses, while gender-specific changes in secretion pathways and protection against colitis are observed in males.

NK2R signaling also influenced the composition of gut bacteria depending on genetic factors and diet, demonstrating the complex interplay between neuropeptide signaling, epithelial function, and host-microbe relationships. These findings suggest that NK2R could be a key molecular switch for intestinal lipid processing and inflammation, and that targeting NK2R with agonists or antagonists may offer sex-specific therapeutic options for metabolic disease and inflammatory bowel disease.