Coenzyme Q10 Supplementation Modulates Hepatic Lipidomic Alterations and Attenuates Metabolic Dysfunction-Associated...

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disorder with limited effective therapeutic options. Emerging lipidomic studies suggest that alterations in membrane-associated lipids contribute to MASH pathophysiology; however, nutritional interventions capable of modifying these lipid alterations remain poorly defined. This study aimed to investigate the effects of coenzyme Q10 (CoQ) supplementation on hepatic lipidomic remodeling in a methionine- and choline-deficient (MCD) diet-induced mouse model of MASH.

Male C57BL/6J mice were fed a methionine- and choline-sufficient diet or an MCD diet for 4 weeks, with MCD-fed mice receiving vehicle or CoQ (100 mg/kg body weight/day). Hepatic lipid profiles were assessed using untargeted LC-MS-based lipidomics, and expression of genes involved in phospholipid and sphingolipid metabolism was quantified by quantitative real-time PCR.

CoQ supplementation significantly attenuated liver injury induced by the MCD diet, as evidenced by reduced histological severity and decreased serum ALT and AST levels. Lipidomic analyses revealed marked alterations in hepatic phospholipid and sphingolipid profiles during MASH development. CoQ was associated with remodeling of phospholipid composition, increasing phosphatidylcholine (PC) species and reducing phosphatidylethanolamine (PE) species, resulting in an increased hepatic PC to PE ratio. This change was accompanied by upregulation of Pemt (phosphatidylethanolamine N-methyltransferase). In contrast, sphingolipid accumulation induced by the MCD diet remained largely unchanged by CoQ, and Smpd1 (sphingomyelin phosphodiesterase 1) expression was not altered.

CoQ supplementation was associated with attenuation of MCD diet-induced MASH and modulation of hepatic phospholipid homeostasis, supporting its potential as a nutritional intervention targeting membrane lipid dysregulation in MASH.