Biomarkers and subtypes of deranged lipid metabolism in nonalcoholic fatty liver disease  

作　　者：José M Mato Cristina Alonso Mazen Noureddin Shelly C Lu 

机构地区：[1]CIC bioGUNE,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd),Technology Park of Bizkaia,Derio 48160,Bizkaia,Spain [2]OWL Metabolomics,Technology Park of Bizkaia,Derio 48160,Bizkaia,Spain [3]Division of Digestive and Liver Diseases,Comprehensive Transplant Center,Cedars-Sinai Medical Center,Los Angeles,CA 90048,United States

出　　处：《World Journal of Gastroenterology》2019年第24期3009-3020,共12页世界胃肠病学杂志（英文版）

摘　　要：Nonalcoholic fatty liver disease(NAFLD)is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy.NAFLD covers a spectrum that ranges from simple steatosis,nonalcoholic steatohepatitis(NASH)with varying degrees of fibrosis,to cirrhosis,which is a major risk factor for hepatocellular carcinoma.Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity,type 2 diabetes mellitus and dyslipidemia,with a global prevalence of 25%.NAFLD arises when the uptake of fatty acids(FA)and triglycerides(TG)from circulation and de novo lipogenesis saturate the rate of FAβ-oxidation and verylow density lipoprotein(VLDL)-TG export.Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH,and therefore,alterations in liver and serum lipidomic signatures are good indicators of the disease’s development and progression.This review focuses on the importance of the classification of NAFLD patients into different subtypes,corresponding to the main alteration(s)in the major pathways that regulate FA homeostasis leading,in each case,to the initiation and progression of NASH.This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments.Nonalcoholic fatty liver disease(NAFLD) is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy. NAFLD covers a spectrum that ranges from simple steatosis, nonalcoholic steatohepatitis(NASH) with varying degrees of fibrosis, to cirrhosis, which is a major risk factor for hepatocellular carcinoma. Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity,type 2 diabetes mellitus and dyslipidemia, with a global prevalence of 25%.NAFLD arises when the uptake of fatty acids(FA) and triglycerides(TG) from circulation and de novo lipogenesis saturate the rate of FA β-oxidation and verylow density lipoprotein(VLDL)-TG export. Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH, and therefore,alterations in liver and serum lipidomic signatures are good indicators of the disease’s development and progression. This review focuses on the importance of the classification of NAFLD patients into different subtypes, corresponding to the main alteration(s) in the major pathways that regulate FA homeostasis leading, in each case, to the initiation and progression of NASH. This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments.

关 键 词：S-ADENOSYLMETHIONINE Methionine adenosyltransferase Lipid METABOLISM Multiomics LIPIDOMICS NONALCOHOLIC STEATOHEPATITIS One-carbon METABOLISM Very low-density LIPOPROTEINS Steatosis Precision medicine 

分 类 号：R[医药卫生]