Glutamine prevents high-fat diet-induced hepatic lipid accumulation in mice by modulating lipolysis and oxidative stress

Abstract Metabolic-associated fatty liver disease (MAFLD) is related to metabolic dysfunction and is characterized by excess fat storage in the liver. Several studies have indicated that glutamine could be closely associated with lipid metabolism disturbances because of its important role in intermediary metabolism. However, the effect of glutamine supplementation on MAFLD progression remains unclear. Here, we used a high-fat diet (HFD)-induced MAFLD C57BL/6 mouse model, and glutamine was supplied in the drinking water at different time points for MAFLD prevention and reversal studies. A MAFLD prevention study was performed by feeding mice an HFD concomitant with 4% glutamine treatment for 24 weeks, whereas the MAFLD reversal study was performed based on 4% glutamine treatment for 13 weeks after feeding mice an HFD for 10 weeks. In the prevention study, glutamine treatment ameliorated serum lipid storage, hepatic lipid injury, and oxidative stress in HFD-induced obese mice, although glutamine supplementation did not affect body weight, glucose homeostasis, energy expenditure, and mitochondrial function. In the MAFLD reversal study, there were no noticeable changes in the basic physiological phenotype and hepatic lipid metabolism. In summary, glutamine might prevent, but not reverse, HFD-induced MAFLD in mice, suggesting that a cautious attitude is required regarding its use for MAFLD treatment.