The Gtpase Arfrp1 Controls Assembly Of Apoa1 To And Lipidation Of Chylomicron In The Golgi Of Intestinal Enterocyte

Intestinal lipid metabolism is comprised of multi-steps of vesicle trafficking. ADP-ribosylation factor-related protein 1 (ARFRP1) regulates protein trafficking between intracellular organelles. To study the role of ARFRP1 in intestinal lipid metabolism, Arfrp1 was deleted in mouse intestine (Arfrp1vil−/−), or depleted by siRNA transfection in Caco-2 cells. Lipid absorption and lipoprotein production were examined. Decreased lipid absorption was detected in oral fat tolerance test in Arfrp1vil−/− mice. However, the apolipoprotein (Apo) B48 and ApoA4 in the plasma were higher, whereas the level of ApoA1 was markedly lower. Fractionation of the plasma showed that the chylomicron fractions of Arfrp1vil−/− mice contain lower triglyceride level, indicating that the Arfrp1vil−/− enterocytes produce a large number of chylomicron particles that are smaller in size containing less fat. Caco-2 cells demonstrated that the defect in Arfrp1 expression caused decreased lipid release, but normal lipid uptake. In conclusion, ARFRP1 plays important roles in chylomicron lipidation in the Golgi and the secretion of ApoA1 in the intestine. Grant Funding Source : Deutsche Forschungsgemeinschaft (Schu 750/5-2; Schu 750/5-3; GRK 1459; SFB958), Alexander von Humboldt Foundation