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 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, PPAR alpha, PPAR gamma, 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.