Uridine prevents fenofibrate-induced fatty liver

Area of Science:

• Biochemistry
• Hepatology
• Pharmacology

Background:

• Uridine (a pyrimidine nucleoside) influences liver lipid metabolism, but its precise targets remain unclear.
• Fenofibrate treatment in mice induces fatty liver by altering NAD(+)/NADH ratio and promoting fatty acid accumulation.

Purpose of the Study:

• To investigate the therapeutic potential of uridine in preventing fenofibrate-induced fatty liver.
• To elucidate the effects of uridine on liver lipid metabolism markers affected by fenofibrate.

Main Methods:

• Utilized a mouse model with fenofibrate-induced fatty liver.
• Administered fenofibrate (400 mg/kg/day) with or without uridine (400 mg/kg/day).
• Assessed liver NAD(+)/NADH ratio, enzyme acetylation (ECHD, ACOX1), and fatty acid levels (LCFA, VLCFA).

Main Results:

• Fenofibrate treatment reduced NAD(+)/NADH ratio, increased ECHD and ACOX1 hyper-acetylation, and accumulated LCFA/VLCFA.
• Uridine co-administration restored NAD(+)/NADH ratio, inhibited ECHD/ACOX1 hyper-acetylation, and reduced LCFA/VLCFA accumulation.

Conclusions:

• Uridine co-administration demonstrates therapeutic potential against fenofibrate-induced fatty liver.
• Uridine effectively modulates key pathways involved in liver lipid metabolism dysregulation.