
-   To clarify whether oxidative stress is involved in the development of hepatocellular preneoplastic foci induced by fenofibrate (FF), a peroxisome proliferator-activated receptor alpha agonist, male F344/N rats were fed a diet containing FF for 13 weeks after N-diethylnitrosamine initiation. Histopathologically, the number of hepatocellular altered foci significantly increased in the FF-treated groups with a concomitant increase in the number of hepatocytes positive for anti-Ki-67 antibody. FF-treatment increased the activity of enzymes such as carnitine acetyltransferase, carnitine palmitoyltransferase, fatty acyl-CoA oxidizing system, and catalase in the liver, but not superoxide dismutase in the liver. In addition, 8-OHdG level in liver DNA, lipofuscin deposition in hepatocytes, and in vitro reactive oxygen species production in microsomes significantly increased due to FF treatment. These results suggest that oxidative stress is involved in the development of FF-induced hepatocellular preneoplastic foci in rats [PMID: 18253720].
-   Emerging evidence suggests that carnitine acetyltransferase enzyme functions as a positive regulator of total body glucose tolerance and muscle activity of pyruvate dehydrogenase (PDH), a mitochondrial enzyme complex that promotes glucose oxidation and is feedback inhibited by acetyl-CoA [PMID: 24395925, PMID: 19553674].

## Summary

The Crat gene's dysregulation in liver diseases and toxicities is closely tied to its function in maintaining metabolic homeostasis, especially under stress [CS: 9]. Crat, encoding carnitine O-acetyltransferase, plays a critical role in the reversible transfer of acyl groups from carnitine to coenzyme A (CoA), regulating the acyl-CoA/CoA ratio [CS: 10]. This regulation is vital in managing energy production and lipid metabolism [CS: 9]. In toxic scenarios, such as with aluminum chloride (AlCl3) exposure leading to oxidative stress and apoptosis in the liver, the upregulation of Crat suggests a protective response [CS: 7]. By transferring acyl groups to CoA, Crat facilitates the transport and beta-oxidation of fatty acids, thereby maintaining mitochondrial function and energy balance during cellular stress [CS: 9].

Moreover, in conditions like fenofibrate-induced hepatocellular preneoplastic foci, characterized by increased reactive oxygen species and oxidative stress, Crat's upregulation aids in managing the elevated demand for efficient fatty acid transport and metabolism [CS: 7]. This is crucial since beta-oxidation of fatty acids is a significant energy source during periods of liver cell regeneration and repair [CS: 8]. The efficient functioning of Crat in these scenarios helps in sustaining energy production, mitigating the accumulation of harmful fatty acids and their metabolites, and supporting liver tissue in coping with and recovering from toxic insults [CS: 8].
