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

Aziz A. Al-Habsi, Andrey Massarsky, Thomas W. Moon

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 3-6. h after exposure.

Fingerprint

Oncorhynchus mykiss
Gene expression
Hepatocytes
Cholesterol
Gene Expression
Peroxisome Proliferator-Activated Receptors
Trout
Biosynthesis
Lipids
Lipid Metabolism
Genes
Xenobiotics
Metabolism
Liver
Fish
Vertebrates
Fishes
Homeostasis
Molecules
Atorvastatin Calcium

Keywords

  • Cholesterol
  • Hepatocytes
  • HMGCR
  • LDL
  • Lipid metabolism
  • Statin drugs

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology

Cite this

@article{13dae0aec0b74e66a62e3528eb828208,
title = "Atorvastatin alters gene expression and cholesterol synthesis in primary rainbow trout (Oncorhynchus mykiss) hepatocytes",
abstract = "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 3-6. h after exposure.",
keywords = "Cholesterol, Hepatocytes, HMGCR, LDL, Lipid metabolism, Statin drugs",
author = "Al-Habsi, {Aziz A.} and Andrey Massarsky and Moon, {Thomas W.}",
year = "2017",
doi = "10.1016/j.cbpb.2017.08.007",
language = "English",
journal = "Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology",
issn = "1096-4959",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Atorvastatin alters gene expression and cholesterol synthesis in primary rainbow trout (Oncorhynchus mykiss) hepatocytes

AU - Al-Habsi, Aziz A.

AU - Massarsky, Andrey

AU - Moon, Thomas W.

PY - 2017

Y1 - 2017

N2 - 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 3-6. h after exposure.

AB - 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 3-6. h after exposure.

KW - Cholesterol

KW - Hepatocytes

KW - HMGCR

KW - LDL

KW - Lipid metabolism

KW - Statin drugs

UR - http://www.scopus.com/inward/record.url?scp=85029701140&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029701140&partnerID=8YFLogxK

U2 - 10.1016/j.cbpb.2017.08.007

DO - 10.1016/j.cbpb.2017.08.007

M3 - Article

JO - Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology

JF - Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology

SN - 1096-4959

ER -