Microcystin-LR Drives Early NAFLD Pathogenesis via Hepatic Cholesterol Accumulation: Dysregulation of <i>Ldlr</i> and <i>Abcg1</i> Expression Uncoupled from <i>Srebp2</i>.

ABSTRACT: Chronic exposure to the cyanotoxin microcystin-LR is an emerging environmental driver of non-alcoholic fatty liver disease (NAFLD); however, the initiating molecular events at sub-lethal, environmentally relevant concentrations remain elusive. Current safety guidelines focus primarily on acute injury, potentially overlooking silent metabolic disruption. The present study investigates the early metabolic toxicity of chronic low-dose microcystin-LR (10 µg/L) in a 7-week rat model, specifically focusing on pre-symptomatic perturbations in lipid homeostasis. By integrating biochemical profiling with multivariate systems toxicology (LASSO and PLS-DA), we identified a specific phenotype of "Silent Hepatic Total Cholesterol Accumulation" (T-CHOL +16%, p = 0.01) occurring in the absence of

SUBMITTER: Kawahara H 

PROVIDER: S-EPMC12945090 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature