King's College London

High-fat diet (HFD) lead to impairment of chylomicrons (CMs) assembly and adversely influences intestinal lipid homeostasis. However, the mechanisms of HFD impairing CMs assembly have yet to be fully understood. Additionally, although choline as a lipid-lowering agent have been widely used, the contribution of choline by functioning as methyl-donor in alleviating HFD-induced intestinal lipid deposition is unknown. Thus, this study was conducted to determine the mechanism of HFD impairing CMs assembly and also tested effect of choline acting as methyl-donor in this process. To this end, in this study four diets (control, HFD, choline and HFD + choline diet) were fed to yellow catfish for 10 weeks in vivo and their intestinal epithelial cells were isolated and incubated for 36 h in fatty acids (FA) with or without choline solution combining si-perk transfection in vitro. The key findings from this study as follows: (1) HFD caused impairment of CMs assembly main by unfolded protein response (UPRer). HFD activated perk and then induced UPRer, which lead to the endoplasmic reticulum dysfunction and further impaired CMs assembly via protein–protein interactions between Perk and Apob48. (2) Choline inhibited the transcriptional expression level of perk via activating -211 CpG methylation site, which initiated the subsequent ameliorating effect on HFD-impaired CMs assembly and intestinal lipid dysfunction. These results provide a new insight into directly crosstalk between UPRer and CMs assembly, and also emphasize the critical contribution of choline acting as a methyl-donor.