FGF15 promotes hepatic NPC1L1 degradation in lithogenic diet-fed mice.

ABSTRACT:

Background

Cholesterol gallstone disease (CGD) is accompanied by biliary cholesterol supersaturation. Hepatic Niemann-Pick C1-like 1 (NPC1L1), which is present in humans but not in wild-type (WT) mice, promotes hepatocyte cholesterol uptake and decreases biliary cholesterol supersaturation. In contrast, intestinal NPC1L1 promotes intestinal cholesterol absorption, increasing biliary cholesterol supersaturation. Ezetimibe (EZE) can inhibit both hepatic and intestinal NPC1L1. However, whether hepatic NPC1L1 can affect CGD progress remains unknown.

Methods

Mice expressing hepatic NPC1L1 (NPC1L1^hepatic-OE mice) were generated using Adeno-associated viruses (AAV) gene delivery. The protein level and function of hepatic NPC1L1 were examined under chow diet, high fat-cho

SUBMITTER: Mo P 

PROVIDER: S-EPMC9547418 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature