Abstract
Alcoholic liver disease is a global health burden and, during its earliest stage, alcoholic steatosis, it is still reversible. Ethanol promotes hepatic lipid accumulation by enhancing lipogenesis and suppressing fatty acid oxidation. The present study investigated whether chalinasterol (CA), a natural compound derived from the seaweed Capsosiphon fulvescens, can attenuate ethanol-induced hepatic steatosis using in vitro hepatocytes and an in vivo mouse model. This revealed that CA significantly reduced ethanol-induced lipid accumulation. While it did not change the expression levels of lipogenesis-related genes or reduce reactive oxygen species levels, suggesting that its protective effect was not mediated through these pathways, it upregulated β-oxidation gene expression and increased phosphorylated AMP-activated protein kinase (AMPK) protein levels. It also reduced ethanol-induced elevated serum alanine transaminase and aspartate transaminase levels, indicating that CA attenuated early liver injury. Therefore, CA alleviated ethanol-induced hepatic steatosis by enhancing fatty acid oxidation through AMPK-peroxisome proliferator-activated receptor alpha activation, highlighting its potential as a preventive intervention for early-stage ALD.