Abstract
Recent deorphanization of several G protein‐coupled receptors (GPRs) as endogenous receptors for free fatty acids (FFARs) has increased our understanding of these nutrients as signaling molecules and the integral role of the gut microbiota in the regulation of host defense mechanisms, energy metabolism, gastrointestinal motility, and secretion. Enteric glial cells and neurotrophins such as BDNF, glial cell line‐derived neurotrophic factor (GDNF) and nerve growth factor (NGF) are essential for the development and integrity of enteric nervous system in the gut. The role of free fatty acid receptors in the regulation of BDNF release from enteric glial cells, however, is not known. Aim. To determine the expression of FFARs and the signaling pathways coupled to FFAR1 and FFAR4, receptors for long chain fatty acids, that mediate BDNF release from enteric glial cells. Results. Quantitative RT‐PCR and western blot studies showed expression of FFAR1, FFAR2, FFAR3, FFAR4 and GPR84 in enteric glial cells; expression of FFAR1, however, was more abundant than other receptors. Linolenic acid which activates FFAR1/FFAR4 caused an increase in phosphoinositide hydrolysis (measured in [3H]myo‐inositol labeled cells), intracellular Ca2+ (measured in Fura‐2 loaded cells) and BDNF release (measured by ELISA). Conclusion. Enteric glial cells express receptors for free fatty acids and activation of FFAR1 and FFAR4 causes BDNF release via stimulation of PLC‐β/IP3/Ca2+ pathway.
Grant Funding Source: Supported by DK34153