Long-chain Fatty Acid-induced Intracellular Signaling in GPR120-expressing Brush Cells at the Limiting Ridge of the Murine Stomach

Brush cells at the gastric groove have been proposed to operate as sensory cells capable of sensing constituents of ingested food. Recent studies have indicated that these cells express GPR120 (also known as FFAR4), the G protein-coupled receptor for long-chain fatty acids (LCFAs). However, functional implications of this receptor in brush cells have remained elusive. Here, we show that a great proportion of brush cells express GPR120. We used phosphorylation of the extracellular signal-regulated kinases 1/2 (ERK1/2) as a readout to monitor brush cell responses to the LCFAs oleic acid and α-linolenic acid. Our results demonstrate that ERK1/2 phosphorylation is increased upon exposure to both fatty acids. Increased ERK1/2 phosphorylation is accompanied by upregulated mRNA and protein levels of cyclooxygenase 2 (COX-2), a key enzyme for prostaglandin biosynthesis. Immunohistochemical experiments confirmed that oleic acid caused ERK1/2 phosphorylation and induced COX-2 expression in brush cells. Our results indicate that LCFA sensing elicits a signaling process in brush cells that may be relevant for a local regulation of gastric functions.