等热量低碳水化合物高蛋白饮食对非酒精性脂肪肝的干预作用

摘要/Abstract

摘要： 目的了解等热量低碳水化合物高蛋白饮食干预NAFLD患者4周后的血清代谢标志物变化及影响。方法选取2019年1月至2020年1月上海中医药大学附属普陀医院就诊的23例NAFLD患者,采用等热量低碳水化合物高蛋白饮食干预4周,在干预前后对脂肪肝患者的血清生化及血脂进行常规检测,并进行代谢组学研究,分析干预前后患者的血清代谢标志物的变化。结果经过4周低碳饮食干预后入组患者体质量、BMI及腰围较前显著下降,分别为74.00(70.75,80.00) kg 比 72.50(69.50,78.25) kg(Z=-3.083,P=0.002);25.63(24.40,26.17) kg/m² 比 24.87(24.27,26.15) kg/m²(Z=-3.389,P=0.001);100.00(91.50,104.00) cm 比 98.00(94.50,100.00) cm(Z=-2.560,P=0.010)。患者肝功能指标ALT、AKP、AST、GGT较前显著下降分别为42.00(30.00,77.50) U/L 比 22.00(14.50,44.00) U/L(Z=-2.875,P=0.004);87.00(81.00,99.50) U/L比78.00(61.00,96.00) U/L(Z=-2.282,P=0.023);30.00(19.00,45.50) U/L 比 22.00(19.00,29.00) U/L(Z=-2.273,P=0.023);35.00(29.50,55.00) U/L 比 29.00(22.00,44.50) U/L(Z=-2.374,P=0.018)。此外,患者TC、GLU水平较前显著下降分别为5.01±1.38 mmol/L 比 3.03±1.56 mmol/L(t=5.002,P<0.01);5.40(5.10,5.50) mmol/L 比 4.50(4.20,4.80) mmol/L(Z=-3.788,P<0.01)。血清代谢组学分析发现干预前后的血清样本能够完全实现分离,同时发现了67个潜在的生物标志物,其中以氨基酸和磷脂代谢类为主。结论等热量低碳水化合物高蛋白饮食方案可以显著减轻NAFLD患者体质量、降低BMI及腰围,改善患者肝功能、血脂及血糖,进一步通过代谢组学发现该饮食方案主要是影响了患者氨基酸与磷脂代谢。

关键词: 非酒精性脂肪肝, 等热量低碳水化合物高蛋白饮食, 血清代谢组学

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

吴小溪, 汪涛, 杜晟楠, 高静静, 蒋元烨, 曹勤. 等热量低碳水化合物高蛋白饮食对非酒精性脂肪肝的干预作用[J]. 肝脏, 2022, 27(6): 688-692.

WU Xiao-xi, WANG Tao, DU Sheng-nan, GAO Jing-jing, JIANG Yuan-ye, CAO Qin. Intervention effect of isocalorie low carbohydrate high protein diet on nonalcoholic fatty liver disease[J]. Chinese Hepatolgy, 2022, 27(6): 688-692.

参考文献

[1] Estes C,Anstee QM,Arias-Loste MT,et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain,United Kingdom, and United States for the period 2016-2030. J Hepatol,2018,69:896-904.
[2] Younossi ZM,Koenig AB,Abdelatif D,et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology,2016,64:73-84.
[3] Mundi MS,Velapati S,Patel J,et al. Evolution of NAFLD and its management.Nutr Clin Pract,2020,35: 72-84.
[4] Schwimmer JB,Ugalde-Nicalo P,Welsh JA,et al. Effect of a low free sugar diet vs usual diet on nonalcoholic fatty liver disease in adolescent boys: a randomized clinical trial. JAMA,2019,321:256-265.
[5] Mittal S,El-Serag HB,Sada YH,et al.Hepatocellular carcinoma in the absence of cirrhosis in united states veterans is associated with nonalcoholic fatty liver disease.Clin Gastroenterol Hepatol,2016,14:124-31.e1.
[6] Castera L,Pinzani M. Non-invasive assessment of liver fibrosis: are we ready? Lancet,2010,375:1419-20.
[7] Alkhouri N,Feldstein AE.Noninvasive diagnosis of nonalcoholic fatty liver disease: are we there yet? Metabolism,2016,65:1087-95.
[8] 非酒精性脂肪性肝病防治指南(2018年更新版).临床肝胆病杂志,2018,34:947-957.
[9] Romero-Gómez M,Zelber-Sagi S,Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol,2017,67:829-846.
[10] Katsagoni CN,Papatheodoridis GV,Ioannidou P,et al. Improvements in clinical characteristics of patients with non-alcoholic fatty liver disease, afteran intervention based on the Mediterranean lifestyle: a randomised controlled clinical trial.Br J Nutr,2018,120:164-175.
[11] Carneros D,López-Lluch G,Bustos M.Physiopathology of lifestyle interventions in Non-Alcoholic Fatty Liver Disease (NAFLD).Nutrients,2020,12:3472.
[12] Zhang HJ,He J,Pan LL,et al. Effects of moderate and vigorous exercise on nonalcoholic fatty liver disease: a randomized clinical trial.JAMA Intern Med,2016,176:1074-82.
[13] Koutoukidis DA,Koshiaris C,Henry JA,et al.The effect of the magnitude of weight loss on non-alcoholic fatty liver disease: a systematic review and meta-analysis.Metabolism,2020,115:154455.
[14] Patel NS,Doycheva I,Peterson MR,et al. Effect of weight loss on magnetic resonance imaging estimation of liver fat and volume in patients with nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol,2015,13: 561-568.
[15] Risi R,Tozzi R,Watanabe M,Beyond weight loss in nonalcoholic fatty liver disease: the role of carbohydrate restriction.Curr Opin Clin Nutr Metab Care,2021,24: 349-353.
[16] Hassani Zadeh S,Mansoori A,Hosseinzadeh M. Relationship between dietary patterns and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Gastroenterol Hepatol,2021,36:1470-1478.
[17] Zou TT,Zhang C,Zhou YF,et al.Lifestyle interventions for patients with nonalcoholic fatty liver disease: a network meta-analysis.Eur J Gastroenterol Hepatol,2018,30:747-755.
[18] Chiarioni G,Popa SL,Dalbeni A,et al.Vegan diet advice might benefit liver enzymes in nonalcoholic fatty liver disease: an open observational pilot study.Journal of gastrointestinal and liver diseases: J Gastrointestin Liver Dis,2021,30:81-87.
[19] 王宇,姜明霞,郑锦锋等.低碳水化合物饮食对非酒精性脂肪肝肥胖患者的影响.东南国防医药,2015,17:5-7.
[20] Yamada K,Mizukoshi E,Seike T,et al. Serum C16:1n7/C16:0 ratio as a diagnostic marker for non-alcoholic steatohepatitis. J Gastroenterol Hepatol,2019,34:1829-1835.
[21] Mahmoudian Dehkordi S,Arnold M,Nho K,et al. Altered bile acid profile associates with cognitive impairment in Alzheimer’s disease-an emerging role for gut microbiome. Alzheimers Dement,2019,15:76-92.
[22] Xie GX,Wang XN,Huang FJ,et al. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis. Int J Cancer,2016,139:1764-75.
[23] Hirsova P,Ibrahim SH,Verma VK,et al. Extracellular vesicles in liver pathobiology: small particles with big impact. Hepatology,2016,64:2219-2233.
[24] Chang Y,Ryu S,Sung E,et al. Higher concentrations of alanine aminotransferase within the reference interval predict nonalcoholic fatty liver disease. Clin Chem,2007,53: 686-692.
[25] Felig P,Marliss E,Cahill Jr GF.Plasma amino acid levels and insulin secretion in obesity.N Engl J Med,1969,281: 811-6.
[26] Moretto M,Kupski C,Mottin CC,et al. Hepatic steatosis in patients undergoing bariatric surgery and its relationship to body mass index and co-morbidities. Obes Surg,2003,13(4):622-624.
[27] Palmer ND,Stevens RD,Antinozzi PA,et al. Metabolomic profile associated with insulin resistance and conversion to diabetes in the Insulin Resistance Atherosclerosis Study. J Clin Endocrinol Metab,2015,100: E463-8.
[28] Dulai PS,Singh S,Patel J,et al. Increased risk of mortality by fibrosis stage in non-alcoholic fatty liver disease: Systematic review and metaanalysis. Hepatology,2017,65:1557-1565.
[29] Rada P,González-Rodríguez ?,García-Monzón C,et al. Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?Cell Death Dis,2020,11:802.
[30] Zhao YL,Vance DE. Phosphatidylcholine and choline homeostasis. J Lipid Res,2008,49:1187-94.
[31] Nakamura T,Nakamura S,Karoji N,et al. Hepatic function tests in heavy drinkers among workmen. Tohoku J Exp Med,1967,93:219-26.
[32] Zhao YL,Agellon LB,Allen TM,et al. The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metab,2006,3:321-331.