Alcohol Induces More Severe Fatty Liver Disease by Influencing Cholesterol Metabolism

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2019 Mar 21

PMID 30891077

Citations 15

Authors

Bo Li

Shan-Shan Lei

Jie Su

Xia-Miao Cai

Hao Xu

Xinglishang He

Ye-Hui Chen

Hai-Xia Lu

He Li

Liu-Qing Qian

Xiang Zheng

Gui-Yuan Lv

Su-Hong Chen

Affiliations

Soon will be listed here.

Abstract

. Fatty liver disease (FLD) is a major cause of morbidity and mortality worldwide. Dietary cholesterol and alcohol consumption are important risk factors for the progression of FLD, but whether and how alcohol induces more severe FLD with cholesterol ingestion remain unclear. Herein, we mainly used the Lieber-DeCarli diet to establish the FLD mouse model to investigate the synergistic effects of alcohol and cholesterol metabolism on liver damage. The indices of aspartate transaminase (AST), alanine transaminase (ALT), low-density lipoprotein cholesterol (LDL-c), and total cholesterol (TC) levels, inflammation foci, and pathogenesis by hematoxylin and eosin (H&E) and Oil Red O staining revealed that alcohol induces more severe liver damage by influencing cholesterol metabolism, which might be primarily related to the influence of cholesterol absorption, synthesis, and excretion on the liver or small intestine. Moreover, inhibition of absorption of intestinal cholesterol, but not of fat, sucrose, and alcohol, absorption into the body's metabolism by Ezetimibe, significantly improved FLD in rats fed with the high fat-cholesterol-sucrose and alcohol diet. These results showed that alcohol plays an important role in cholesterol metabolism in FLD.

Citing Articles

Bioinformatics based exploration of the anti-NAFLD mechanism of Wang's empirical formula via TLR4/NF-κB/COX2 pathway.

Chen S, Zhou C, Huang J, Qiao Y, Wang N, Huang Y Mol Med. 2024; 30(1):278.

PMID: 39730994 PMC: 11673956. DOI: 10.1186/s10020-024-01022-3.

NLRP3 activation maintains intestinal epithelial barrier and reduces liver injury in alcoholic liver disease mice.

Li S, Wang Y, Xie Z, Wang Y, Feng Z, Xu J Clin Transl Med. 2024; 14(12):e70099.

PMID: 39605303 PMC: 11602754. DOI: 10.1002/ctm2.70099.

Metabolomics analyses reveal the liver-protective mechanism of Wang's metabolic formula on metabolic-associated fatty liver disease.

Chen S, Huang J, Huang Y, Zhou C, Wang N, Zhang L Heliyon. 2024; 10(13):e33418.

PMID: 39040343 PMC: 11261804. DOI: 10.1016/j.heliyon.2024.e33418.

Polysaccharides from Oliv. Leaves Alleviate Acute Alcoholic Liver Injury by Modulating the Microbiota-Gut-Liver Axis in Mice.

Li Y, Wang H, Leng X, Gao J, Li C, Huang D Foods. 2024; 13(7).

PMID: 38611393 PMC: 11011369. DOI: 10.3390/foods13071089.

Emerging Diagnostics and Therapeutics for Non-alcoholic Fatty Liver Disease.

Darbhanga J, Krulikowski K, Riskin S Cureus. 2023; 15(10):e47821.

PMID: 38021846 PMC: 10676744. DOI: 10.7759/cureus.47821.

References

Latour M, Patterson B, Kitchens R, Ostlund Jr R, Hopkins D, Schonfeld G . Effects of alcohol and cholesterol feeding on lipoprotein metabolism and cholesterol absorption in rabbits. Arterioscler Thromb Vasc Biol. 1999; 19(3):598-604. DOI: 10.1161/01.atv.19.3.598. View

Chen J, Goodart S, Cooper A . Mice expressing the human CYP7A1 gene in the mouse CYP7A1 knock-out background lack induction of CYP7A1 expression by cholesterol feeding and have increased hypercholesterolemia when fed a high fat diet. J Biol Chem. 2002; 277(45):42588-95. DOI: 10.1074/jbc.M205117200. View

Achliya G, Wadodkar S, Dorle A . Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats. J Ethnopharmacol. 2004; 90(2-3):229-32. DOI: 10.1016/j.jep.2003.09.037. View

Nanji A, Dannenberg A, Jokelainen K, Bass N . Alcoholic liver injury in the rat is associated with reduced expression of peroxisome proliferator-alpha (PPARalpha)-regulated genes and is ameliorated by PPARalpha activation. J Pharmacol Exp Ther. 2004; 310(1):417-24. DOI: 10.1124/jpet.103.064717. View

Yu L, Gupta S, Xu F, Liverman A, Moschetta A, Mangelsdorf D . Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion. J Biol Chem. 2004; 280(10):8742-7. DOI: 10.1074/jbc.M411080200. View

Crabb D, Liangpunsakul S . Alcohol and lipid metabolism. J Gastroenterol Hepatol. 2006; 21 Suppl 3:S56-60. DOI: 10.1111/j.1440-1746.2006.04582.x. View

Konig B, Koch A, Spielmann J, Hilgenfeld C, Stangl G, Eder K . Activation of PPARalpha lowers synthesis and concentration of cholesterol by reduction of nuclear SREBP-2. Biochem Pharmacol. 2006; 73(4):574-85. DOI: 10.1016/j.bcp.2006.10.027. View

Yin H, Kim M, Kim J, Kong G, Kang K, Kim H . Differential gene expression and lipid metabolism in fatty liver induced by acute ethanol treatment in mice. Toxicol Appl Pharmacol. 2007; 223(3):225-33. DOI: 10.1016/j.taap.2007.06.018. View

Deushi M, Nomura M, Kawakami A, Haraguchi M, Ito M, Okazaki M . Ezetimibe improves liver steatosis and insulin resistance in obese rat model of metabolic syndrome. FEBS Lett. 2007; 581(29):5664-70. DOI: 10.1016/j.febslet.2007.11.023. View

10.

Huang Z, Zhou X, Nicholson A, Gotto Jr A, Hajjar D, Han J . Activation of peroxisome proliferator-activated receptor-alpha in mice induces expression of the hepatic low-density lipoprotein receptor. Br J Pharmacol. 2008; 155(4):596-605. PMC: 2518458. DOI: 10.1038/bjp.2008.331. View

11.

Purohit V, Gao B, Song B . Molecular mechanisms of alcoholic fatty liver. Alcohol Clin Exp Res. 2008; 33(2):191-205. PMC: 2633431. DOI: 10.1111/j.1530-0277.2008.00827.x. View

12.

Farfan Labonne B, Gutierrez M, Gomez-Quiroz L, Fainstein M, Bucio L, Souza V . Acetaldehyde-induced mitochondrial dysfunction sensitizes hepatocytes to oxidative damage. Cell Biol Toxicol. 2009; 25(6):599-609. DOI: 10.1007/s10565-008-9115-5. View

13.

Ioannou G, Morrow O, Connole M, Lee S . Association between dietary nutrient composition and the incidence of cirrhosis or liver cancer in the United States population. Hepatology. 2009; 50(1):175-84. DOI: 10.1002/hep.22941. View

14.

Zelcer N, Hong C, Boyadjian R, Tontonoz P . LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science. 2009; 325(5936):100-4. PMC: 2777523. DOI: 10.1126/science.1168974. View

15.

Hu M, Wang F, Li X, Rogers C, Liang X, Finck B . Regulation of hepatic lipin-1 by ethanol: role of AMP-activated protein kinase/sterol regulatory element-binding protein 1 signaling in mice. Hepatology. 2011; 55(2):437-46. PMC: 3253249. DOI: 10.1002/hep.24708. View

16.

Savard C, Tartaglione E, Kuver R, Haigh W, Farrell G, Subramanian S . Synergistic interaction of dietary cholesterol and dietary fat in inducing experimental steatohepatitis. Hepatology. 2012; 57(1):81-92. PMC: 5341743. DOI: 10.1002/hep.25789. View

17.

Kosenko T, Golder M, Leblond G, Weng W, Lagace T . Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation. J Biol Chem. 2013; 288(12):8279-8288. PMC: 3605646. DOI: 10.1074/jbc.M112.421370. View

18.

Bertola A, Mathews S, Ki S, Wang H, Gao B . Mouse model of chronic and binge ethanol feeding (the NIAAA model). Nat Protoc. 2013; 8(3):627-37. PMC: 3788579. DOI: 10.1038/nprot.2013.032. View

19.

Xie G, Zhong W, Li H, Li Q, Qiu Y, Zheng X . Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption. FASEB J. 2013; 27(9):3583-93. PMC: 3752538. DOI: 10.1096/fj.13-231860. View

20.

Ushio M, Nishio Y, Sekine O, Nagai Y, Maeno Y, Ugi S . Ezetimibe prevents hepatic steatosis induced by a high-fat but not a high-fructose diet. Am J Physiol Endocrinol Metab. 2013; 305(2):E293-304. DOI: 10.1152/ajpendo.00442.2012. View