中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 36 Issue 5
May  2020
Turn off MathJax
Article Contents

Research advances in nonalcoholic fatty liver disease in lean individuals

DOI: 10.3969/j.issn.1001-5256.2020.05.046
  • Published Date: 2020-05-20
  • The incidence rate of nonalcoholic fatty liver disease(NAFLD) is continuously increasing in the world, and NAFLD is a major cause of chronic liver disease in developed countries such as the United States and may become the most common chronic liver disease in China in the future. NAFLD is often observed in the obese population; however, it is also commonly seen in lean individuals. This article summarizes the latest studies on lean NAFLD and elaborates on the following pathogeneses of this disease: the change in single nucleotide polymorphism is one of the predisposing factors for NAFLD in the lean population; the change of gut microbiota and sarcopenia may induce a variety of metabolic disorders including hyperlipidemia, hyperuricemia, insulin resistance, and iron metabolic disorders, and such metabolic disorders may promote the development of NAFLD; in addition, unhealthy dietary habits and lifestyle may contribute to the accumulation of fat and increase the burden of the liver. The combined effect of these factors eventually lead to the development of NAFLD, but further studies are still needed to clarify the pathogenesis of lean NAFLD.

     

  • loading
  • [1] ANDRONESCU CI,PURCAREA MR,BABES PA. Nonalcoholic fatty liver disease:Epidemiology, pathogenesis and therapeutic implications[J]. J Med Life, 2018, 11(1):20-23.
    [2] CHALASANI N, YOUNOSSI Z, LAVINE JE, et al. The diagnosis and management of non-alcoholic fatty liver disease:Practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases,and American College of Gastroenterology[J]. Gastroenterology, 2012, 55(6):2005-2023.
    [3] YOUNOSSI ZM, KOENIG AB, ABDELATIF D, et al. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology, 2016, 64(1):73-84.
    [4] PERUMPAIL BJ, ALI KM, YOO ER, et al. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease[J].World J Gastroenterol, 2017, 23(47):8263-8276.
    [5] CHING-YEUNG YB, KWOK D, WONG VW. Magnitude of nonalcoholic fatty liver disease:Eastern perspective[J]. J Clin Exp Hepatol, 2019, 9(4):491-496.
    [6] HUANG JF, TSAI PC, YEH ML, et al. Risk stratification of nonalcoholic fatty liver disease across body mass index in a community basis[J]. J Formos Med Assoc, 2020, 119(1 Pt 1):89-96.
    [7] ESTES C, ANSTEE QUENTIN M, 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]. J Hepatol, 2018, 69(4):896-904.
    [8] KUMAR R, MOHAN S. Non-alcoholic fatty liver disease in lean subjects:Characteristics and implications[J]. J Clin Transl Hepatol, 2017, 5(3):216-223.
    [9] BORRELLI A, BONELLI P, TUCCILLO FM, et al. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma:Current and innovative therapeutic approaches[J]. Redox Biology, 2018,15:467-479.
    [10] SHI YW, WANG QY, SUN YM, et al. The prevalence of lean/nonobese nonalcoholic fatty liver disease:A systematic review and meta-analysis[J]. J Clin Gastroenterol, 2019.[Online ahead of print]
    [11] LIU CJ. Prevalence and risk factors for non-alcoholic fatty liver disease in Asian people who are not obese[J]. J Gastroenterol Hepatol, 2012, 27(10):1555-1560.
    [12] DAS K, DAS K, MUKHERJEE PS, et al. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant disease[J]. Hepatology, 2010, 51(5):1593-602.
    [13] FENG RN, DU SS, WANG C, et al. Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population[J]. World J Gastroenterol,2014, 20(47):17932-17940.
    [14] LEE SW, LEE TY, YANG SS, et al. Risk factors and metabolic abnormality of patients with non-alcoholic fatty liver disease:Either non-obese or obese Chinese population[J]. Hepatobiliary Pancreat Dis Int, 2018, 17(1):45-48.
    [15] NADERIAN M, KOLAHDOOZAN S, SHARIFI AS, et al. Assessment of lean patients with nonalcoholic fatty liver disease in a middle income country; prevalence and its association with metabolic disorders:A cross-sectional study[J]. Arch Iran Med, 2017, 20(4):211-217.
    [16] HAGSTRÖM H, NASR P, EKSTEDT M, et al. Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease:A long-term follow-up study[J]. Hepatol Commun, 2017, 2(1):48-57.
    [17] GONZALEZ-CANTERO J, MARTIN-RODRIGUEZ JL, GONZALEZ-CANTERO A, et al. Insulin resistance in lean and overweight non-diabetic Caucasian adults:Study of its relationship with liver triglyceride content, waist circumference and BMI[J]. PLoS One, 2018, 13(2):e0192663.
    [18] SUCCURRO E, MARINI MA, FRONTONI S, et al. Insulin secretion in metabolically obese, but normal weight, and in metabolically healthy but obese individuals[J]. Obesity(Silver Spring), 2008, 16(8):1881-1886.
    [19] TU LN, SHOWALTER MR, CAJKA T, et al. Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice[J]. Sci Rep, 2017, 7(1):6120.
    [20] TOBARI M, HASHIMOTO E, TANIAI M, et al. Characteristics of non-alcoholic steatohepatitis among lean patients in Japan:Not uncommon and not always benign[J]. J Gastroenterol Hepatol, 2019, 34(8):1404-1410.
    [21] SOOKOIAN S, PIROLA CJ. Systematic review with meta-analysis:Risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients[J]. Aliment Pharmacol Ther,2017, 46(2):85-95.
    [22] LI H, CHEN Y, TIAN X, et al. Comparison of clinical characteristics between lean and obese nonalcoholic fatty liver disease in the northeast Chinese population[J]. Arch Med Sci Atheroscler Dis, 2019, 4:e191-e195.
    [23] KUMAR R, RASTOGI A, SHARMA MK, et al. Clinicopathological characteristics and metabolic profiles of non-alcoholic fatty liver disease in Indian patients with normal body mass index:Do they differ from obese or overweight non-alcoholic fatty liver disease?[J]. Indian J Endocrinol Metab, 2013, 17(4):665-671.
    [24] MARGARITI E, DEUTSCH M, MANOLAKOPOULOS S, et al.Non-alcoholic fatty liver disease may develop in individuals with normal body mass index[J]. Ann Gastroenterol, 2012,25(1):45-51.
    [25] NERVOSA ROSEN E, BAKSHI N, WATTERS A, et al. Hepatic complications of anorexia nervosa[J]. Dig Dis Sci, 2017, 62(11):2977-2981.
    [26] ZHOU Y, WEI F, FAN Y. High serum uric acid and risk of nonalcoholic fatty liver disease:A systematic review and meta-analysis[J]. Clin Biochem, 2016, 49(7-8):636-642.
    [27] ZHENG X, GONG L, LUO R, et al. Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese adults[J]. Lipids Health Dis, 2017, 16(1):202.
    [28] DARMAWAN G, HAMIJOYO L, HASAN I. Association between serum uric acid and non-alcoholic fatty liver disease:A Metaanalysis[J]. Acta Med Indones, 2017, 49(2):136-147.
    [29] ANDERSON GJ, VULPE CD. Mammalian iron transport[J].Cell Mol Life Sci, 2009, 66(20):3241-3261.
    [30] AKYUZ U, YESIL A, YILMAZ Y. Characterization of lean patients with nonalcoholic fatty liver disease:Potential role of high hemoglobin levels[J]. Scand J Gastroenterol, 2015, 50(3):341-346.
    [31] PEVERILL W, POWELL LW, SKOIEN R. Evolving concepts in the pathogenesis of NASH:Beyond steatosis and inflammation[J]. Int J Mol Sci, 2014, 15(5):8591-8638.
    [32] BUZZETTI E, PINZANI M, TSOCHATZIS EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease(NAFLD)[J]. Metabolism, 2016, 65(8):1038-1048.
    [33] VIRKAMAKI A, KORSHENINNIKOVA E, SEPPALA-LINDROOS A, et al. Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle[J].Diabetes, 2001, 50(10):2337-2343.
    [34] GONZALEZ-CANTERO J, MARTIN-RODRIGUEZ JL, GONZALEZ-CANTERO A, et al. Insulin resistance in lean and overweight non-diabetic Caucasian adults:Study of its relationship with liver triglyceride content, waist circumference and BMI[J]. PLoS One, 2018, 13(2):e0192663.
    [35] WEI JL, LEUNG JC, LOONG TC, et al. Prevalence and severity of nonalcoholic fatty liver disease in non-obese patients:A population study using proton-magnetic resonance spectroscopy[J]. Am J Gastroenterol, 2015, 110(9):1306-1315.
    [36] BUGIANESI E, GASTALDELLI A, VANNI E, et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease:Sites and mechanisms[J]. Diabetologia, 2005,48(4):634-642.
    [37] LEE YH, JUNG KS, KIM SU, et al. Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance:Nationwide surveys(KNHANES 2008-2011)[J]. J Hepatol,2015, 63(2):486-493.
    [38] LEE MJ, KIM EH, BAE SJ, et al. Age-related decrease in skeletal muscle mass is an independent risk factor for incident nonalcoholic fatty liver disease:A 10-year retrospective cohort study[J]. Gut Liver, 2019, 13(1):67-76.
    [39] BULL MJ, PLUMMER NT. Part 1:The human gut microbiome in health and disease[J]. Integr Med(Encinitas), 2014, 13(6):17-22.
    [40] DUARTE SMB, STEFANO JT, MIELE L. Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake:A prospective pilot study[J]. Nutr Metab Cardiovasc Dis, 2018, 28(4):369-387.
    [41] ZHOU YJ, LI YY, NIE YQ, et al. Prevalence of fatty liver disease and its risk factors in the population of South China[J].World J Gastroenterol, 2007, 13(47):6419-6424.
    [42] MOFIDI F, POUSTCHI H, YARI Z, et al. Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease:A pilot, randomised, double-blind, placebo-controlled, clinical trial[J]. Br J Nutr, 2017, 117(5):662-668.
    [43] KWAK JH, JUN DW, LEE SM, et al. Lifestyle predictors of obese and non-obese patients with nonalcoholic fatty liver disease:A cross-sectional study[J]. Clin Nutr, 2018, 37(5):1550-1557.
    [44] TU LN, SHOWALTER MR, CAJKA T, et al. Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice[J]. Sci Rep, 2017, 7(1):6120.
    [45] PETERSEN KF, DUFOUR S, HARIRI A, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease[J]. N Engl J Med, 2010, 362(12):1082-1089.
    [46] YUAN X, WATERWORTH D, PERRY JR, et al. Populationbased genome-wide association studies reveal six loci influencing plasma levels of liver enzymes[J]. Am J Hum Genet,2008, 83(4):520-528.
    [47] ROMEO S, KOZLITINA J, XING C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease[J]. Nat Genet, 2008, 40(12):1461-1465.
    [48] SHEN J, WONG GL, CHAN HL, et al. PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome[J]. Aliment Pharmacol Ther, 2014, 38(5):532-539.
    [49] SOOKOIAN S, PIROLA CJ. Systematic review with meta-analysis:The significance of histological disease severity in lean patients with nonalcoholic fatty liver disease[J]. Aliment Pharmacol Ther, 2018, 47(1):16-25.
    [50] MATTEONI CA, YOUNOSSI ZM, GRAMLICH T, et al. Nonalcoholic fatty liver disease:A spectrum of clinical and pathological severity[J]. Gastroenterology, 1999, 116(6):1413-1419.
    [51] YOUNES R, BUGIANESI E. NASH in lean individuals[J]. Semin Liver Dis, 2019, 39(1):86-95.
    [52] ALAM S, JAHID HASAN M, KHAN MAS, et al. Effect of weight reduction on histological activity and fibrosis of lean nonalcoholic steatohepatitis patient[J]. J Transl Int Med, 2019, 7(3):106-114.
    [53] IPSEN DH, ROLIN B, RAKIPOVSKI G, et al. Liraglutide decreases hepatic inflammation and injury in advanced lean non-alcoholic steatohepatitis[J]. Basic Clin Pharmacol Toxicol, 2018, 123(6):704-713.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (731) PDF downloads(248) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return