Advances on the association of vitamin A and chronic liver diseases

doi:10.3877/cma.j.issn.1674-1358.2024.02.001

Abstract

Abstract:

Chronic liver diseases (CLDs) have become one of the diseases with high morbidity and mortality worldwide. Vitamin A (Vit A) is an essential fat-soluble vitamin. Retinoic acid (RA), an active metabolite of Vit A, is a potent regulator of numerous biological pathways via the RA signaling pathway acting as binding to RA receptors (RARs). Liver is the primary organ for Vit A storage and metabolism in humans. A body of evidence shows that reductions in liver Vit A, aberrant Vit A metabolism, and dysregulated in RA signaling are implicated in numerous diseases of liver. Conversely, restoration of RA signaling, pharmacological treatments with natural and synthetic retinoids, and newer agonists for specific RARs show promising benefits for treatment of a number of liver diseases. However, the pathogenesis remains incompletely understood. Here we provide a comprehensive review of the literature demonstrating a role for Vit A in limiting the pathogenesis of these diseases and in the treatment of liver diseases, in order to provide a new perspective for research and treatment of CLDs.

Key words: Vitamin A, Retinoic acid receptor, Chronic liver diseases, Nonalcoholic fatty liver disease, Alcoholic liver disease, Viral hepatitis, Liver fibrosis, Hepatocellular carcinoma

Min Li, Shiying Yang, Xiaoqin Gao, Dan Zhou, Xiao Tang, Liting Zhang. Advances on the association of vitamin A and chronic liver diseases[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2024, 18(02): 65-70.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhsyhlcgrbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-1358.2024.02.001

https://zhsyhlcgrbzz.cma-cmc.com.cn/EN/Y2024/V18/I02/65

References 46

[1]	Devarbhavi H, Asrani SK, Arab JP, et al. Global burden of liver disease: 2023 update[J]. J Hepatol,2023,79(2):516-537.
[2]	Ghyselinck NB, Duester G. Retinoic acid signaling pathways[J]. Development,2019,146(13):dev167502.
[3]	Melis M, Tang XH, Trasino SE, et al. Retinoids in the pathogenesis and treatment of liver diseases[J]. Nutrients,2022,14(7):1456.
[4]	Li B, Cai SY, Boyer JL. The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology[J]. Biochim Biophys Acta Mol Basis Dis,2021,1867(5):166085.
[5]	Li Y, Wong K, Walsh K, et al. Retinoic acid receptor β stimulates hepatic induction of fibroblast growth factor 21 to promote fatty acid oxidation and control whole-body energy homeostasis in mice[J]. J Biol Chem,2013,288(15):10490-10504.
[6]	Trasino SE, Tang XH, Jessurun J, et al. Retinoic acid receptor β2 agonists restore glycaemic control in diabetes and reduce steatosis[J]. Diabetes Obes Metab,2016,18(2):142-151.
[7]	Melis M, Tang XH, Trasino SE, et al. Effects of AM80 compared to AC261066 in a high fat diet mouse model of liver disease[J]. PLoS One,2019,14(1):e0211071.
[8]	Tang XH, Melis M, Lu C, et al. A retinoic acid receptor β2 agonist attenuates transcriptome and metabolome changes underlying nonalcohol-associated fatty liver disease[J]. J Biol Chem,2021,297(6):101331.
[9]	Byrne CD, Targher G. What’s new in NAFLD pathogenesis, biomarkers and treatment?[J]. Nat Rev Gastroenterol Hepatol, 2020,17(2):70-71.
[10]	Sanyal AJ. Past, present and future perspectives in nonalcoholic fatty liver disease[J]. Nat Rev Gastroenterol Hepatol,2019,16(6):377-386.
[11]	Parlati L, Régnier M, Guillou H, et al. New targets for NAFLD[J]. JHEP Rep,2021,3(6):100346.
[12]	Friedman SL, Neuschwander-Tetri BA, Rinella M, et al. Mechanisms of NAFLD development and therapeutic strategies[J]. Nat Med,2018,24(7):908-922.
[13]	Tilg H, Adolph TE, Dudek M, et al. Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity[J]. Nat Metab,2021,3(12):1596-1607.
[14]	Blaner WS, O’Byrne SM, Wongsiriroj N, et al. Hepatic stellate cell lipid droplets: A specialized lipid droplet for retinoid storage[J]. Biochim Biophys Acta,2009,1791(6):467-473.
[15]	Haaker MW, Vaandrager AB, Helms JB. Retinoids in health and disease: A role for hepatic stellate cells in affecting retinoid levels[J]. Biochim Biophys Acta Mol Cell Biol Lipids,2020,1865(6):158674.
[16]	Geng C, Xu H, Zhang Y, et al. Retinoic acid ameliorates high-fat diet-induced liver steatosis through sirt1[J]. Sci China Life Sci,2017,60(11):1234-1241.
[17]	Saeed A, Dullaart RPF, Schreuder TCMA, et al. Disturbed vitamin A metabolism in non-alcoholic fatty liver disease (NAFLD)[J]. Nutrients,2017,10(1):29.
[18]	Yang D, Vuckovic MG, Smullin CP, et al. Modest decreases in endogenous all-trans-retinoic acid produced by a mouse rdh10 heterozygote provoke major abnormalities in adipogenesis and lipid metabolism[J]. Diabetes,2018,67(4):662-673.
[19]	Sharpton SR, Schnabl B, Knight R, et al. Current concepts, opportunities, and challenges of gut microbiome-based personalized medicine in nonalcoholic fatty liver disease[J]. Cell Metab,2021, 33(1):21-32.
[20]	Kolodziejczyk AA, Zheng D, Shibolet O, et al. The role of the microbiome in NAFLD and NASH[J]. EMBO Mol Med,2019, 11(2):e9302.
[21]	Nicoletti A, Ponziani FR, Biolato M, et al. Intestinal permeability in the pathogenesis of liver damage: From non-alcoholic fatty liver disease to liver transplantation[J]. World J Gastroenterol,2019, 25(33):4814-4834.
[22]	Li Y, Gao Y, Cui T, et al. Retinoic acid facilitates toll-like receptor 4 expression to improve intestinal barrier function through retinoic acid receptor beta[J]. Cell Physiol Biochem,2017,42(4):1390-1406.
[23]	Dunn W, Shah VH. Pathogenesis of alcoholic liver disease[J]. Clin Liver Dis,2016,20(3):445-456.
[24]	Ferdouse A, Agrawal RR, Gao MA, et al. Alcohol induced hepatic retinoid depletion is associated with the induction of multiple retinoid catabolizing cytochrome P450 enzymes[J]. PLoS One,2022, 17(1):e0261675.
[25]	Melis M, Tang XH, Attarwala N, et al. A retinoic acid receptor β2 agonist protects against alcohol liver disease and modulates hepatic expression of canonical retinoid metabolism genes[J]. Biofactors, 2022,48(2):469-480.
[26]	Kane MA, Folias AE, Wang C, et al. Ethanol elevates physiological all- trans -retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity[J]. FASEB J,2010,24(3):823-832.
[27]	Ganne-Carrié N, Nahon P. Hepatocellular carcinoma in the setting of alcohol-related liver disease[J]. J Hepatol,2019,70(2):284-293.
[28]	Diesinger T, Buko V, Lautwein A, et al. Drug targeting CYP2E1 for the treatment of early-stage alcoholic steatohepatitis[J]. PLoS One,2020,15(7):e0235990.
[29]	Tang XH, Melis M, Mai K, et al. Fenretinide improves intestinal barrier function and mitigates alcohol liver disease[J]. Front Pharmacol,2021,12:630557.
[30]	Yeom S, Kim SS, Jeong H, et al. Hepatitis B virus X protein activates E3 ubiquitin ligase Siah-1 to control virus propagation via a negative feedback loop[J]. J Gen Virol,2017,98(7):1774-1784.
[31]	Han J, Jang KL. All-trans retinoic acid inhibits hepatitis B virus replication by downregulating HBx levels via Siah-1-mediated proteasomal degradation[J]. Viruses,2023,15(7):1456.
[32]	Kwak J, Shim JH, Tiwari I, et al. Hepatitis C virus core protein inhibits E6AP expression via DNA methylation to escape from ubiquitin-dependent proteasomal degradation[J]. Cancer Lett,2016,380(1):59-68.
[33]	Chen C, Pan D, Deng AM, et al. DNA methyltransferases 1 and 3B are required for hepatitis C virus infection in cell culture[J]. Virology,2013,441(1):57-65.
[34]	Lee HK, Yoon H, Jang KL. All-trans retinoic acid inhibits HCV replication by downregulating core levels via E6AP-mediated proteasomal degradation[J]. Biochem Biophys Res Commun, 2022,594:15-21.
[35]	Nagel M, Labenz C, Dobbermann H, et al. Suppressed serological vitamin A in patients with liver cirrhosis is associated with impaired liver function and clinical detoriation[J]. Eur J Gastroenterol Hepatol,2022,34(10):1053-1059.
[36]	Simbrunner B, Semmler G, Stadlmann A, et al. Vitamin A levels reflect disease severity and portal hypertension in patients with cirrhosis[J]. Hepatol Int,2020,14(6):1093-1103.
[37]	Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol,2021,18(3):151-166.
[38]	Trasino SE, Tang XH, Jessurun J, et al. A retinoic acid receptor β2 agonist reduces hepatic stellate cell activation in nonalcoholic fatty liver disease[J]. J Mol Med (Berl),2016,94(10):1143-1151.
[39]	Radaeva S, Wang L, Radaev S, et al. Retinoic acid signaling sensitizes hepatic stellate cells to NK cell killing via upregulation of NK cell activating ligand RAE1[J]. Am J Physiol Gastrointest Liver Physiol,2007,293(4):G809-G816.
[40]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2021,71(3):209-249.
[41]	Younossi Z, Stepanova M, Ong JP, et al. Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates[J]. Clin Gastroenterol Hepatol,2019,17(4):748-755. e3.
[42]	Datfar T, Doulberis M, Papaefthymiou A, et al. Viral hepatitis and hepatocellular carcinoma: state of the art[J]. Pathogens, 2021,10(11):1366.
[43]	Chen Z, Tian R, She Z, et al. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease[J]. Free Radic Biol Med,2020,152:116-141.
[44]	Irshad M, Gupta P, Irshad K. Immunopathogenesis of liver injury during hepatitis C virus infection[J]. Viral Immunol,2019,32(3):112- 120.
[45]	Cortes E, Lachowski D, Rice A, et al. Retinoic acid receptor-βis downregulated in hepatocellular carcinoma and cirrhosis and its expression inhibits myosin-driven activation and durotaxis in hepatic stellate cells[J]. Hepatology,2019 69(2):785-802.
[46]	Liao XH, Zhang AL, Zheng M, et al. Chemical or genetic Pin1 inhibition exerts potent anticancer activity against hepatocellular carcinoma by blocking multiple cancer-driving pathways[J]. Sci Rep,2017,7(1):43639.

Please choose a citation manager

Content to export