Affiliation:
1. Soochow University
2. The Second Hospital of Hebei Medical University
3. First Affiliated Hospital of Soochow University
Abstract
Abstract
Saturated fatty acid (SFA) and unsaturated fatty acid (UFA) have distinct impacts on health. Whether SFA and UFA are differentially transported in liver remains elusive. Here, we find the secretion of UFA but not SFA esters is retarded in a hepatic endoplasmic reticulum (ER) stress model. Amoug 13 members of protein disulfide isomerase (PDI) family, only PDIA1 (PDI) deficiency leads to hepatosteatosis and hypolipidemia. In PDI-deficient liver, there is a severe accumulation but secretory blockade of UFA esters, whereas the accumulation and secretion of SFA esters remain normal. PDI catalyzes the oxidative folding of microsomal triglyceride transfer protein (MTP). In addition, PDI deficiency impairs the assembly and secretion of Apolipoprotein B-100 (ApoB-100) very low-density lipoprotein (VLDL) but not ApoB-48 VLDL. In summary, we find that the secretion of UFA esters is PDI-MTP indispensable, while SFA esters could be transferred out of liver via ApoB-48 VLDL through a PDI-MTP-independent pathway.
Publisher
Research Square Platform LLC
Reference70 articles.
1. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies;Souza RJ;BMJ,2015
2. DeWitt E, Dysinger I, Larmer Z, Kolwicz SC Jr (2019) High Saturated and Unsaturated Fat Diets Yield Different Disease Phenotypes in Mice. The FASEB Journal 33, 755.753-755.753
3. Saturated and Unsaturated Dietary Fats Differentially Modulate Ethanol-Induced Changes in Gut Microbiome and Metabolome in a Mouse Model of Alcoholic Liver Disease;Kirpich IA;Am J Pathol,2016
4. Excesive consumption of unsaturated fatty acids leads to oxidative and inflammatory instability in Wistar rats;Grujic-Milanovic JD;Biomed Pharmacother,2021
5. Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat-a randomized controlled dietary intervention study;Ulven SM;Am J Clin Nutr,2019