Abstract: Objective Ultra performance liquid chromatography tandem high resolution mass spectrometry (UPLC-Q-Orbitrap/MS) was used to explore the changes of serum metabolic markers in patients with NAFLD after 4 weeks of isocalorie low carbohydrate and high protein diet intervention. The purpose was to find more suitable dietary recommendations for NAFLD patients in China.Methods 23 patients with NAFLD from January 2019 to January 2020 in our hospital were selected as the research objects. They were intervened with isocalorie low carbohydrate and high protein diet for 4 weeks. Before and after the intervention, the serum biochemical and blood lipid of patients were detected routinely, and the metabonomics was conducted. The changes of serum metabolic markers before and after the intervention were analyzed.Results After 4 weeks of low-carbon diet intervention, the weight, BMI and waist circumference of the enrolled patients were significantly reduced compared with the previous, [74.00(70.75-80.00) kg vs 72.50(69.50-78.25) kg, Z=-3.083, P=0.002; 25.63(24.40-26.17) kg/m² vs 24.87(24.27-26.15) kg/m², Z=-3.389, P=0.001; 100.00(91.50-104.00) cm vs 98.00(94.50-100.00) cm, Z=-2.560, P= 0.010]. In terms of serum biochemistry, the patients’ ALT level were significantly lower than before [42.00(30.00-77.50) U/L vs 22.00(14.50-44.00) U/L, Z=-2.875, P=0.004], AKP, AST, GGT were decreased [87.00(81.00-99.50) U/L vs 78.00(61.00-96.00) U/L, Z=-2.282, P=0.023; 30.00(19.00-45.50) U/L vs 22.00(19.00-29.00) U/ L, Z=-2.273, P=0.023; 35.00(29.50-55.00) U/L vs 29.00(22.00-44.50) U/L, Z=-2.374, P=0.018]. In addition, the patients’ TC and GLU levels were significantly decreased (5.01±1.38 mmol/L vs 3.03±1.56 mmol/L, t=5.002, P=0.000; 5.40 (5.10-5.50) mmol/L vs 4.50 (4.20-4.80) mmol/L, Z=-3.788, P=0.000]. Serum metabonomics analysis found that the serum samples before and after the intervention could be completely separated, with significant differences. At the same time, 67 potential biomarkers were found, of which amino acid and phospholipid metabolism were the main ones.Conclusion In this study, the isocaloric low carbohydrate high protein diet can significantly reduce the body weight, BMI and waist circumference of patients with NAFLD, also improve the liver function, blood lipid and blood glucose of patients, and further through metabonomics, we find that the diet mainly affects the metabolism of amino acids and phospholipids.

Key words: Non-alcoholic fatty liver, Isocaloric low carbohydrate high protein diet, Serum metabolomics