sensing of fatty acids for octanoylation of ghrelin involves a gustatory g-protein传感的脂肪酸octanoylation激素包括味觉g蛋白.pdfVIP

Sensing of Fatty Acids for Octanoylation of Ghrelin Involves a Gustatory G-Protein 1 1 2 1 1 Sara Janssen , Jorien Laermans , Hiroshi Iwakura , Jan Tack , Inge Depoortere * 1Translational Research Center for Gastrointestinal Disorders, Catholic University of Leuven, Leuven, Belgium, 2 Departments of Medicine, Clinical Science, Endocrinology, and Metabolism, Translational Research Center, Kyoto University Graduate School of Medicine, Kyoto University Hospital, Kyoto, Japan Abstract Background: Ghrelin is an important regulator of energy – and glucose homeostasis. The octanoylation at Ser3 is essential for ghrelin’s biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, a-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell. Methods: Wild-type (WT) and a-gustducin knockout (gust2/ 2) mice were fed a glyceryl trioctanoate-enriched diet (OD) during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or a-gustducin/a-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo. Results: Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust2/ 2 mice. Gastric emptying was accelerated in WT but not in gust2/ 2 mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, a-gustducin or a-transducin pos