Gastric neuropeptide W is regulated by meal-related nutrients

• NPW mRNA expression in the gastric mucosa increases in response to protein and glucose feeding.
• Plasma concentrations of NPW do not change after nutrient ingestion.
• Protein but not glucose directly induces NPW expression in gastric antral mucosal cells.
• Calcium-sensing receptor may be involved in gastric NPW expression.

Neuropeptide W (NPW) is secreted from gastrin (G) cells in the stomach in response to food intake. The mechanisms underlying food intake-induced regulation of gastric NPW is largely unknown. We hypothesized that specific macronutrients were responsible for food-induced NPW secretion. We evaluated the acute effects of fat, carbohydrate and protein on plasma NPW concentrations in humans and mice. The effect of different nutrients on expression of NPW in the antral stomach was also determined in mice. Primary cell cultures of mouse gastric antral mucosal cells were used to investigate the signaling pathway of NPW expression. Plasma NPW concentrations did not change after nutrient ingestion in either humans or mice. NPW mRNA expression and the number of NPW positive cells in the mouse antrum were increased in mice gavage fed with protein or glucose, but not lipid. In primary antral mucosal cell culture, NPW mRNA expression was stimulated by l-phenylalanine, but not glucose. Calcium-sensing receptor (CaSR) positive cells were largely co-localized with NPW in mouse gastric antral mucosal cells, and NPW mRNA expression was inhibited by a selective antagonist of CaSR NPS2143. However, the l-phenylalanine-induced increase in NPW expression was not affected by NPS2143. In conclusion, these studies indicated an inconsistency between plasma and gastric NPW expression in response to nutrient ingestion, suggesting food induced gastric NPW expression may play a more important role locally. Moreover, glucose and especially protein are potent regulators of gastric NPW, via distinct mechanisms.