Biomarkers and Subtypes of Deranged Lipid Metabolism in Non-alcoholic Fatty Liver Disease

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2019 Jul 12

PMID 31293337

Citations 90

Authors

Jose M Mato

Cristina Alonso

Mazen Noureddin

Shelly C Lu

Affiliations

Soon will be listed here.

Abstract

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 very-low 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.

Citing Articles

Non-alcoholic fatty liver disease development: A multifactorial pathogenic phenomena.

Bashir A, Duseja A, De A, Mehta M, Tiwari P Liver Res. 2025; 6(2):72-83.

PMID: 39958625 PMC: 11791825. DOI: 10.1016/j.livres.2022.05.002.

Practical Approaches to Managing Dyslipidemia in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

Bril F, Berg G, Barchuk M, Nogueira J J Lipid Atheroscler. 2025; 14(1):5-29.

PMID: 39911965 PMC: 11791423. DOI: 10.12997/jla.2025.14.1.5.

Association between serum uric acid-to-high-density lipoprotein cholesterol ratio and metabolic dysfunction-associated steatotic liver disease among Chinese children with obesity.

Liu M, Cao B, Luo Q, Song Y, Liu K, Wu D Front Endocrinol (Lausanne). 2025; 15():1474384.

PMID: 39845880 PMC: 11750666. DOI: 10.3389/fendo.2024.1474384.

Evaluation of autoimmune phenomena in patients with nonalcoholic fatty liver disease on the basis of liver pathology.

Zhu Y, Zhang Y, Rao Y, Jiang Y, Liu Y, Li J World J Hepatol. 2025; 16(12):1407-1416.

PMID: 39744192 PMC: 11686539. DOI: 10.4254/wjh.v16.i12.1407.

Higher levels of plasmatic saturated fatty acid were significantly associated with liver fibrosis in HIV mono-infection: A case-control study.

Almeida C, Arantes Ferreira Peres W, Silva P, Santos de Aguiar Cardoso C, de Andrade M, Castro-Alves J Metabol Open. 2024; 24:100334.

PMID: 39717737 PMC: 11664064. DOI: 10.1016/j.metop.2024.100334.

References

Sanyal A, Mirshahi F, Rizzo W, Contos M, Sterling R, Luketic V . Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001; 120(5):1183-92. DOI: 10.1053/gast.2001.23256. View

Lu S, Alvarez L, Huang Z, Chen L, An W, Corrales F . Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation. Proc Natl Acad Sci U S A. 2001; 98(10):5560-5. PMC: 33252. DOI: 10.1073/pnas.091016398. View

Diraison F, Moulin P, Beylot M . Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease. Diabetes Metab. 2003; 29(5):478-85. DOI: 10.1016/s1262-3636(07)70061-7. View

Gibbons G, Wiggins D, Brown A, Hebbachi A . Synthesis and function of hepatic very-low-density lipoprotein. Biochem Soc Trans. 2004; 32(Pt 1):59-64. DOI: 10.1042/bst0320059. View

Bugianesi E, Gastaldelli A, Vanni E, Gambino R, Cassader M, Baldi S . Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia. 2005; 48(4):634-42. DOI: 10.1007/s00125-005-1682-x. View

Donnelly K, Smith C, Schwarzenberg S, Jessurun J, Boldt M, Parks E . Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005; 115(5):1343-51. PMC: 1087172. DOI: 10.1172/JCI23621. View

Anstee Q, Goldin R . Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Pathol. 2006; 87(1):1-16. PMC: 2517349. DOI: 10.1111/j.0959-9673.2006.00465.x. View

Oz H, Im H, Chen T, de Villiers W, McClain C . Glutathione-enhancing agents protect against steatohepatitis in a dietary model. J Biochem Mol Toxicol. 2006; 20(1):39-47. PMC: 3006092. DOI: 10.1002/jbt.20109. View

Li Z, Agellon L, Allen T, Umeda M, Jewell L, Mason A . The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metab. 2006; 3(5):321-31. DOI: 10.1016/j.cmet.2006.03.007. View

10.

Luka Z, Capdevila A, Mato J, Wagner C . A glycine N-methyltransferase knockout mouse model for humans with deficiency of this enzyme. Transgenic Res. 2006; 15(3):393-7. PMC: 2792375. DOI: 10.1007/s11248-006-0008-1. View

11.

Cuchel M, Bloedon L, Szapary P, Kolansky D, Wolfe M, Sarkis A . Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007; 356(2):148-56. DOI: 10.1056/NEJMoa061189. View

12.

Marra F, Gastaldelli A, Svegliati Baroni G, Tell G, Tiribelli C . Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol Med. 2008; 14(2):72-81. DOI: 10.1016/j.molmed.2007.12.003. View

13.

Fabbrini E, Mohammed B, Magkos F, Korenblat K, Patterson B, Klein S . Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease. Gastroenterology. 2008; 134(2):424-31. PMC: 2705923. DOI: 10.1053/j.gastro.2007.11.038. View

14.

Martinez-Chantar M, Vazquez-Chantada M, Ariz U, Martinez N, Varela M, Luka Z . Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology. 2008; 47(4):1191-9. PMC: 2405897. DOI: 10.1002/hep.22159. View

15.

Bonnefont-Rousselot D, Condat B, Sassolas A, Chebel S, Bittar R, Federspiel M . Cryptogenic cirrhosis in a patient with familial hypocholesterolemia due to a new truncated form of apolipoprotein B. Eur J Gastroenterol Hepatol. 2008; 21(1):104-8. DOI: 10.1097/MEG.0b013e3282ffd9f8. View

16.

Chakravarthy M, Lodhi I, Yin L, Malapaka R, Xu H, Turk J . Identification of a physiologically relevant endogenous ligand for PPARalpha in liver. Cell. 2009; 138(3):476-88. PMC: 2725194. DOI: 10.1016/j.cell.2009.05.036. View

17.

Fujita K, Nozaki Y, Wada K, Yoneda M, Fujimoto Y, Fujitake M . Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis. Hepatology. 2009; 50(3):772-80. DOI: 10.1002/hep.23094. View

18.

Arrese E, Soulages J . Insect fat body: energy, metabolism, and regulation. Annu Rev Entomol. 2009; 55:207-25. PMC: 3075550. DOI: 10.1146/annurev-ento-112408-085356. View

19.

Guillou H, Zadravec D, Martin P, Jacobsson A . The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice. Prog Lipid Res. 2009; 49(2):186-99. DOI: 10.1016/j.plipres.2009.12.002. View

20.

Virtue S, Vidal-Puig A . Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome--an allostatic perspective. Biochim Biophys Acta. 2010; 1801(3):338-49. DOI: 10.1016/j.bbalip.2009.12.006. View