New approaches of N-acetylcysteine on fatty acid transport and metabolism in a rat model of MASLD induced by high-fat diet

Abstract The number of individuals suffering from metabolic dysfunction-associated steatotic liver disease (MASLD) has increased. The worldwide occurrence of fatty liver diseases is estimated to affect between 30% and 38% of adults from all races, ethnic group and sex in diet dependent manner, positioning these conditions as leading causes of chronic liver diseases. It is crucial to identify a natural substance that can safeguard against alterations in the lipid balance. There is a significant amount of research indicating that n-acetylcysteine (NAC) helps prevent inflammation and lipid deposition in peripheral tissues. The aim of this study was to investigate the effects of NAC on lipid metabolism and fatty acid composition in the liver of rats fed a high-fat diet (HFD). An experiment was conducted on male Wistar rats that received a standard diet or an HFD, divided into 4 groups ( n = 6). Half of the rats from the Control and HFD groups received and intragastrically NAC solution. After 8 weeks of experimental procedures, rats were anaesthetized, and the liver tissue was used for further analysis. Gas-liquid chromatography was used to determine the content of total lipid fractions and fatty acid composition in each fraction. Western blot and real-time PCR methods were used to measure the expression of protein or mRNA of fatty acid (FA) transporters and enzymes that regulated lipid metabolism. NAC decreased FA transport into hepatocytes by a decline in the expression of FATP2, FABPpm, and CD36. Supplementation of NAC also significantly reduced elongation of C16:0, PA to C18:0 and enlarged the C20:0/C18:0 elongation ratio with simultaneous enhancement in C20:5 n-3, EPA and C22:6 n-3, DHA levels. Based on our results, we concluded that NAC point anti-inflammatory and pro-resolving properties, suggesting its potential role in the limitation of the development of simple steatosis changes by altering lipid disruption in rats receiving a high-fat diet.