Characterization of Free Fatty Acid Receptor 4 and Its Involvement in Nutritional Control and Immune Response in Pacific Oysters (Crassostrea gigas)

[Image: see text] Free fatty acid receptor 4 (FFAR4) has various physiological functions, including energy regulation and immunological homeostasis. We examined the only FFAR4 homologue in the Pacific oyster Crassostrea gigas (CgFFAR4), which functions as a sensor of long-chain fatty acids. CgFFAR4 is 1098 bp long and contains a seven-transmembrane G protein-coupled receptor domain. CgFFAR4 expression was high in the hepatopancreas, but it was downregulated after fasting, indicating that it plays an essential role in food digestion. Lipopolysaccharide stimulation downregulated CgFFAR4 level, probably as an immune response of the animal. Reduced glycogen level alongside decreased insulin receptor, insulin receptor substrate, and C. gigas glycogen synthase transcription levels after CgFFAR4 knockdown revealed that CgFFAR4 was involved in the regulation of fatty acid and glycogen levels via the insulin pathway. Accordingly, this is the first study on an invertebrate FFAR and provides new insights into the role of this receptor in immune response and nutritional control.