等热量低碳水化合物高蛋白饮食对非酒精性脂肪性肝病血清脂质的影响

Effect of an isocaloric high-protein low-carbohydrate diet on serum lipid profile in nonalcoholic fatty liver disease

目的 研究等热量低碳水化合物高蛋白饮食(CRD)对非酒精性脂肪性肝病(NAFLD)患者的影响及形成的脂质代谢差异。方法 收集2019年1月—2022年6月在上海市普陀区中心医院消化内科诊断为NAFLD的患者25例与健康志愿者25例,NAFLD患者采用CRD干预。采集受试者基本信息,检测肝功能、血脂等生化指标,使用超高效液相色谱串联高分辨质谱(UPLC-Q-Orbitrap/MS)技术进行血清脂质分析。主成分分析(PCA)和正交偏最小二乘判别法(OPLS-DA)用于分析血清脂质代谢标志物。结果 经过4周的饮食干预后,患者的体质量由(77.88±10.76) kg降至(76.62±10.78) kg,(P<0.001)、体质指数(BMI)由25.63(24.40-26.80)kg/m^(2)降低至24.88(24.5-26.34)kg/m^(2)(P<0.01)、腰围无显著性变化(P>0.05)。CRD干预后NAFLD患者AKP水平[(3.12±23.90) U/L]显著低于干预前[(93.36±30.41) U/L],(P<0.01)。GGT、ALT水平分别由干预前的(43.84±27.78) U/L、35.0(25.0-76.5)U/L降低至(35.16±17.51) U/L和28.0(14.5-45.5)U/L(均P<0.05)。患者血清TC水平由4.56(3.82-6.31)mmol/L降低至3.15(1.79-4.32)mmol/L(P<0.001)。CHE、AST、TG、HDL、LDL水平无显著变化(均P>0.05)。脂质组学研究发现,CRD干预后,血清中OAFHA、LPC、MG、LPG、PI、PS、PG、PA和SM的含量发生显著变化(P<0.05)。结论 CRD干预可以减轻NAFLD患者体质量、降低BMI和腰围,改善患者肝功能和血脂异常。脂质组学分析表明,CRD饮食能缓解脂肪肝脂毒性、调控鞘脂代谢进而改善NAFLD的发生、发展。本次研究发现的53个脂质成分亦可作为NAFLD的生物标志物。

Objective To study the effects of an isocaloric low-carbohydrate high-protein diet(CRD)[2]on patients with nonalcoholic fatty liver disease(NAFLD)and its impact on lipid metabolism.Methods Twenty-five patients diagnosed with NAFLD and 25 healthy volunteers from the physical examination center were recruited for the study.The NAFLD patients underwent a CRD intervention.Basic information about the subjects was collected,and biochemical indices,including liver function and blood lipids,were tested.Serum lipid analysis was performed using UPLC-Q-Orbitrap/MS technology.Principal component analysis and orthogonal partial least squares-discriminant analysis were utilized to construct differential serum lipid metabolic profiles and identify lipid biomarkers.Results After 4 weeks of dietary intervention,the patients'weight decreased from 77.88±10.76 kg to 76.62±10.78 kg,(P<0.001),and BMI decreased from^(2)5.63(24.40-26.80)kg/m^(2) to 24.88(24.5-26.34)kg/m^(2),(P<0.01),while waist circumference showed no significant change(P>0.05).The AKP level significantly decreased from 93.36±30.41U/L to 3.12±23.90 U/L after CRD intervention(P<0.01).GGT and ALT levels were reduced from 43.84±27.78 U/L and 35.0(25.0-76.5)U/L to 35.16±17.51 U/L and 28.0(14.5-45.5)U/L respectively(P<0.05 for both).Serum TC levels decreased significantly from 4.56(3.82-6.31)mmol/L to 3.15(1.79-4.32)mmol/L(P<0.001).There were no significant changes in the levels of CHE,AST,TG,HDL,and LDL(P>0.05).Lipidomic studies revealed significant changes in serum levels of OAFHA,LPC,MG,LPG,PI,PS,PG,PA,and SM after CRD intervention(P<0.05).Conclusion The CRD intervention effectively reduce body mass,lower BMI and waist circumference,and improve liver function and dyslipidemia in patients with NAFLD.Lipidomic analysis indicated that a CRD diet could mitigate the development of NAFLD by alleviating fatty liver lipotoxicity and regulating sphingolipid metabolism.The 53 lipid biomarkers identified through this screening can serve as potential targets for NAFLD intervention.