Alcohol intake remains the most important cause of
fatty liver throughout the world. The current study was undertaken to determine whether dietary supplementation with Codonopsis lanceolata root water extract attenuates the development of
alcoholic fatty liver in rats and to elucidate the molecular mechanism for such an effect. Male Sprague-Dawley rats were fed normal diet (ND),
ethanol diet (ED) (36% of total energy from
ethanol), or 0.5% C. lanceolata root extract-supplemented
ethanol diet (ED+C) for 8 weeks. C. lanceolata root water extract supplemented to rats with chronic alcohol consumption ameliorated the
ethanol-induced accumulations of hepatic
cholesterol and
triglyceride. Chronic alcohol consumption up-regulated the hepatic expression of genes involved in
inflammation,
fatty acid synthesis, and
cholesterol metabolism, including
tumor necrosis factor alpha (
TNFalpha),
liver X receptor alpha (LXRalpha),
sterol regulatory element-binding protein (SREBP)-1c,
fatty acid synthase,
acetyl-coenzyme A carboxylase alpha (ACC),
stearoyl-coenzyme A desaturase 1,
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), and
low-density lipoprotein receptor (LDLR). The
ethanol-induced up-regulations of
TNFalpha, LXRalpha,
SREBP-1c, HMGR, and LDLR genes in the liver were reversed by feeding C. lanceolata root water extract for 8 weeks. Moreover,
ethanol-induced decreases in the ratio of phospho-5'-AMP-activated
protein kinase (AMPK) alpha/AMPKalpha and phospho-ACC/ACC
protein levels in the liver were significantly restored (135% and 35% increases, respectively, P < .05) by supplementing them with C. lanceolata root water extract. In conclusion, C. lanceolata root water extract appears to be protective against
alcoholic fatty liver through the regulation of
SREBP-1c, LXRalpha, HMGR, and LDLR genes and by the phosphorylation of AMPKalpha and ACC, which are implicated in lipid metabolism.