Atorvastatin alters gene expression and cholesterol synthesis in primary rainbow trout (Oncorhynchus mykiss) hepatocytes

The liver is a key metabolic organ contributing significantly to both lipid and cholesterol homeostasis in vertebrates. This study examines whether the human pharmaceutical atorvastatin (ATV), which is designed to lower cholesterol biosynthesis, could disrupt lipid dynamics in fish. The study invest...

Full description

Saved in:
Bibliographic Details
Published in:Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology 2018-10, Vol.224, p.262-269
Main Authors: Al-Habsi, Aziz A., Massarsky, Andrey, Moon, Thomas W.
Format: Article
Language:English
Subjects:
Animals
Atorvastatin Calcium - pharmacology
Cholesterol
Cholesterol - metabolism
Fish Proteins - biosynthesis
Gene Expression Regulation - drug effects
Hepatocytes
Hepatocytes - metabolism
HMGCR
LDL
Lipid metabolism
Lipid Metabolism - drug effects
Oncorhynchus mykiss - metabolism
Statin drugs
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The liver is a key metabolic organ contributing significantly to both lipid and cholesterol homeostasis in vertebrates. This study examines whether the human pharmaceutical atorvastatin (ATV), which is designed to lower cholesterol biosynthesis, could disrupt lipid dynamics in fish. The study investigates the effects of ATV at a physiologically relevant exposure regimen (concentration and duration) on gene transcripts and the biosynthesis of cholesterol and other lipid and non-lipid molecules in primary rainbow trout hepatocytes. Trout hepatocytes exposed to ATV increased the transcript abundance of genes involved in lipid metabolism (HMGCR1, LDLR, PPARα, PPARγ, and SREBP1) and xenobiotic metabolism (CYP3A27), and reduced cholesterol synthesis. This study demonstrates that lipid metabolism in trout hepatocytes is sensitive to the effects of ATV, and changes in gene expression occur within 3–6h after exposure.
ISSN:1096-4959
1879-1107
DOI:10.1016/j.cbpb.2017.08.007