Sortilin restricts secretion of apolipoprotein B-100 by hepatocytes under stressed but not basal conditions.

ABSTRACT: Genetic variants at the SORT1 locus in humans, which cause increased SORT1 expression in the liver, are significantly associated with reduced plasma levels of LDL cholesterol and apolipoprotein B (apoB). However, the role of hepatic sortilin remains controversial, as genetic deletion of sortilin in mice has resulted in variable and conflicting effects on apoB secretion. Here, we found that Sort1-KO mice on a chow diet and several Sort1-deficient hepatocyte lines displayed no difference in apoB secretion. When these models were challenged with high-fat diet or ER stress, the loss of Sort1 expression resulted in a significant increase in apoB-100 secretion. Sort1-overexpression studies yielded reciprocal results. Importantly, carriers of SORT1 variant with diabetes had larger decreases in pl

SUBMITTER: Conlon DM 

PROVIDER: S-EPMC8920325 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature