Dietary Choline Mitigates High-Fat Diet-Impaired Chylomicrons Assembly via UPRer Modulated by perk DNA Methylation

TY - JOUR

T1 - Dietary Choline Mitigates High-Fat Diet-Impaired Chylomicrons Assembly via UPRer Modulated by perk DNA Methylation

AU - Bai, Zhen Yu

AU - Zheng, Hua

AU - Luo, Zhi

AU - Hogstrand, Christer

AU - Wang, Ling Jiao

AU - Song, Yu Feng

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022/12

Y1 - 2022/12

N2 - High-fat diets (HFD) lead to impairment of chylomicrons (CMs) assembly and adversely influence 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, has been widely used and its deficiency has been closely linked to non-alcoholic steatohepatitis (NASH), the contribution of choline by functioning as a 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 the effect of choline acting as a 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 led to 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 the −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 direct crosstalk between UPRer and CMs assembly, and also emphasize the critical contribution of choline acting as a methyl donor and shed new light on choline-deficient diet-induced NASH.

AB - High-fat diets (HFD) lead to impairment of chylomicrons (CMs) assembly and adversely influence 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, has been widely used and its deficiency has been closely linked to non-alcoholic steatohepatitis (NASH), the contribution of choline by functioning as a 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 the effect of choline acting as a 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 led to 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 the −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 direct crosstalk between UPRer and CMs assembly, and also emphasize the critical contribution of choline acting as a methyl donor and shed new light on choline-deficient diet-induced NASH.

KW - Apob48

KW - choline

KW - chylomicrons

KW - high-fat diet

KW - methylation

KW - perk

UR - http://www.scopus.com/inward/record.url?scp=85143682372&partnerID=8YFLogxK

U2 - 10.3390/cells11233848

DO - 10.3390/cells11233848

M3 - Article

C2 - 36497107

AN - SCOPUS:85143682372

SN - 2073-4409

VL - 11

JO - Cells

JF - Cells

IS - 23

M1 - 3848

ER -