The Effect of Sterol Regulatory Element-Binding Protein-1 C Modification on Fatty Acids in Alcoholic Liver Disease (ALD)

Authors

  • Ali Hussein lafta Department of Biochemistry, College of Medicine, University of Thi Qar, Iraq.
  • Hussain Ahmed Shamkhi Department of Biochemistry, College of Medicine, University of Thi Qar, Iraq.

Abstract

Abstract : Among chronic liver diseases, alcoholic liver disease (ALD) is the most common in the
world. The main cause of ALD is excessive alcohol consumption. The accumulation of fatty acids in
liver cells is one of the oldest and most famous alcohol-related changes that cause the development of
ALD . Although the mechanism by which excessive alcohol intake leads to fatty acid accumulation is
far-fetched and complex, one of the mechanisms by which alcohol affects fatty acids is the regulation
of the sterol regulatory element-binding protein-1 c (SREBP-1 C) which may be key to the treatment of
ALD. In this review, we present evidence supporting the key important role of the SREBP-1 C in
influencing the synthesis and accumulation of fatty acids that are a major cause of ALD, and we
suggest that there should be future studies to evaluate the modification of the SREBP-1 C as a possible
new treatment for alcoholic liver disease.

References

J. S. Bajaj, “Alcohol, liver disease and the gut microbiota,” Nat. Rev. Gastroenterol. Hepatol.,

vol. 16, no. 4, pp. 235–246, 2019.

Y. Ha, I. Jeong, and T. H. Kim, “Alcohol-related liver disease: an overview on pathophysiology,

diagnosis and therapeutic perspectives,” Biomedicines, vol. 10, no. 10, p. 2530, 2022.

J. D. Stanaway et al., “Global, regional, and national comparative risk assessment of 84

behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries

and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Stu,” Lancet, vol.

, no. 10159, pp. 1923–1994, 2018.

J. Manthey, K. D. Shield, M. Rylett, O. S. M. Hasan, C. Probst, and J. Rehm, “Global alcohol

exposure between 1990 and 2017 and forecasts until 2030: a modelling study,” Lancet, vol. 393, no.

, pp. 2493–2502, 2019.

F. Zhong et al., “Complement C3 activation regulates the production of tRNA-derived fragments

Gly-tRFs and promotes alcohol-induced liver injury and steatosis,” Cell Res., vol. 29, no. 7, pp. 548–

, 2019.

P. Sharma and A. Arora, “Clinical presentation of alcoholic liver disease and non-alcoholic fatty

liver disease: spectrum and diagnosis,” Transl. Gastroenterol. Hepatol., vol. 5, 2020.

M.-J. Xu, Z. Zhou, R. Parker, and B. Gao, “Targeting inflammation for the treatment of alcoholic

liver disease,” Pharmacol. Ther., vol. 180, pp. 77–89, 2017.

J. Xu et al., “Blockade of IL-17 signaling reverses alcohol-induced liver injury and excessive

alcohol drinking in mice. JCI insight. 2020; 5 (3): e131277.” .

S. Yoshiya et al., “Blockade of the apelin–APJ system promotes mouse liver regeneration by

activating Kupffer cells after partial hepatectomy,” J. Gastroenterol., vol. 50, no. 5, pp. 573–582, 2015,

doi: 10.1007/s00535-014-0992-5.

S. A. Phillips, K. Osborn, C.-L. Hwang, A. Sabbahi, and M. R. Piano, “Ethanol induced

oxidative stress in the vasculature: friend or foe,” Curr. Hypertens. Rev., vol. 16, no. 3, pp. 181–191,

M. Ran et al., “Alcohol-induced autophagy via upregulation of PIASy promotes HCV replication

in human hepatoma cells. Cell Death Dis 9: 898.” 2018.

B. Wang et al., “Protective effects of curcumin against chronic alcohol-induced liver injury in

mice through modulating mitochondrial dysfunction and inhibiting endoplasmic reticulum stress,”

Food Nutr. Res., vol. 63, 2019.

X. H. Han, J. Y. Wang, and P. Y. Zheng, “Attenuation and mechanism of endoplasmic reticulum

stress-mediated hepatocyte apoptosis in rats with alcohol-induced liver injury by qinggan huoxue recipe

and its disassembled formulas,” Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi Jiehe Zazhi=

Chinese J. Integr. Tradit. West. Med., vol. 31, no. 5, pp. 653–658, 2011.

J. Fan, “Epidemiology of alcoholic and nonalcoholic fatty liver disease in C hina,” J.

Gastroenterol. Hepatol., vol. 28, pp. 11–17, 2013.

H. A. EDMONDSON, R. L. PETERS, H. H. FRANKEL, and S. BOROWSKY, “The early stage

of liver injury in the alcoholic,” Medicine (Baltimore)., vol. 46, no. 2, pp. 119–129, 1967.

M. Dugum and A. McCullough, “Diagnosis and management of alcoholic liver disease,” J. Clin.

Transl. Hepatol., vol. 3, no. 2, p. 109, 2015.

K. Rasineni and C. A. Casey, “Molecular mechanism of alcoholic fatty liver,” Indian J.

Pharmacol., vol. 44, no. 3, pp. 299–303, 2012.

J. Zhou, Z. Jiang, C. Zhao, Z. Zhen, W. Wang, and A. A. Nanji, “Long‐term binge and escalating

ethanol exposure causes necroinflammation and fibrosis in rat liver,” Alcohol. Clin. Exp. Res., vol. 37,

no. 2, pp. 213–222, 2013.

T. Zeng and K.-Q. Xie, “Ethanol and liver: recent advances in the mechanisms of ethanolinduced hepatosteatosis,” Arch. Toxicol., vol. 83, pp. 1075–1081, 2009.

R. S. O’shea, S. Dasarathy, A. J. McCullough, and P. G. C. of the A. A. for the S. of L. D. and

the P. P. C. of the A. C. of Gastroenterology, “Alcoholic liver disease,” Hepatology, vol. 51, no. 1, pp.

–328, 2010.

P. Puri et al., “Alcohol consumption is associated with the severity and outcome of acute liver

injury/failure,” Liver Int., vol. 40, no. 2, pp. 360–367, 2020.

Y.-H. Yoon and C. M. Chen, “Surveillance Report# 105: Liver cirrhosis mortality in the United

States: National, state, and regional trends, 2000–2013,” Natl. Inst. Alcohol Abus. Alcohol. (NIAAA),

Bethesda, MD, 2016.

K. Shield et al., “National, regional, and global burdens of disease from 2000 to 2016

attributable to alcohol use: a comparative risk assessment study,” Lancet Public Heal., vol. 5, no. 1, pp.

e51–e61, 2020.

C. A. Marroni et al., “Liver transplantation and alcoholic liver disease: History, controversies,

and considerations,” World J. Gastroenterol., vol. 24, no. 26, p. 2785, 2018.

S. Mitra, A. De, and A. Chowdhury, “Epidemiology of non-alcoholic and alcoholic fatty liver

diseases,” Transl. Gastroenterol. Hepatol., vol. 5, 2020.

J. Rehm, A. V Samokhvalov, and K. D. Shield, “Global burden of alcoholic liver diseases,” J.

Hepatol., vol. 59, no. 1, pp. 160–168, 2013.

N. Sheron, “Alcohol and liver disease in Europe–Simple measures have the potential to prevent

tens of thousands of premature deaths,” J. Hepatol., vol. 64, no. 4, pp. 957–967, 2016.

P. S. Mukherjee et al., “Etiology and mode of presentation of chronic liver diseases in India: A

multi centric study,” PLoS One, vol. 12, no. 10, p. e0187033, 2017.

M. D. Glantz et al., “The epidemiology of alcohol use disorders cross-nationally: Findings from

the World Mental Health Surveys,” Addict. Behav., vol. 102, p. 106128, 2020.

H. Li, E. Toth, and N. J. Cherrington, “Alcohol metabolism in the progression of human

nonalcoholic steatohepatitis,” Toxicol. Sci., vol. 164, no. 2, pp. 428–438, 2018.

M. G. Neuman et al., “Alcoholic liver disease: a synopsis of the Charles Lieber’s Memorial

Symposia 2009–2012,” Alcohol Alcohol., vol. 49, no. 4, pp. 373–380, 2014.

S. Zakhari, “Overview: how is alcohol metabolized by the body?,” Alcohol Res. Heal., vol. 29,

no. 4, p. 245, 2006.

C. S. Lieber, “Ethanol metabolism, cirrhosis and alcoholism,” Clin. Chim. acta, vol. 257, no. 1,

pp. 59–84, 1997.

T.-M. Leung and N. Nieto, “CYP2E1 and oxidant stress in alcoholic and non-alcoholic fatty liver

disease,” J. Hepatol., vol. 58, no. 2, pp. 395–398, 2013.

C. Heier, H. Xie, and R. Zimmermann, “Nonoxidative ethanol metabolism in humans—from

biomarkers to bioactive lipids,” IUBMB Life, vol. 68, no. 12, pp. 916–923, 2016.

T. M. Maenhout, M. L. De Buyzere, and J. R. Delanghe, “Non-oxidative ethanol metabolites as a

measure of alcohol intake,” Clin. Chim. Acta, vol. 415, pp. 322–329, 2013.

J. Hyun, J. Han, C. Lee, M. Yoon, and Y. Jung, “Pathophysiological aspects of alcohol

metabolism in the liver,” Int. J. Mol. Sci., vol. 22, no. 11, p. 5717, 2021.

A. Louvet and P. Mathurin, “Alcoholic liver disease: mechanisms of injury and targeted

treatment,” Nat. Rev. Gastroenterol. Hepatol., vol. 12, no. 4, pp. 231–242, 2015.

B. Guo and Z. Li, “Endoplasmic reticulum stress in hepatic steatosis and inflammatory bowel

diseases,” Front. Genet., vol. 5, p. 102163, 2014.

N. A. Osna et al., “Aberrant post-translational protein modifications in the pathogenesis of

alcohol-induced liver injury,” World J. Gastroenterol., vol. 22, no. 27, p. 6192, 2016.

R.-B. Ding et al., “Protective effect of panax notoginseng saponins on acute ethanol-induced

liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated

oxidative stress,” J. Agric. Food Chem., vol. 63, no. 9, pp. 2413–2422, 2015.

S. J. Lee et al., “New potential biomarker proteins for alcoholic liver disease identified by a

comparative proteomics approach,” J. Cell. Biochem., vol. 118, no. 5, pp. 1189–1200, 2017.

R. A. Ansari, K. Husain, and S. A. A. Rizvi, “Role of transcription factors in steatohepatitis and

hypertension after ethanol: the epicenter of metabolism,” Biomolecules, vol. 6, no. 3, p. 29, 2016.

L. Yang et al., “Lipophagy and alcohol-induced fatty liver,” Front. Pharmacol., vol. 10, p. 495,

H.-D. Li et al., “Wogonin attenuates inflammation by activating PPAR-γ in alcoholic liver

disease,” Int. Immunopharmacol., vol. 50, pp. 95–106, 2017.

M. Galicia-Moreno and G. Gutiérrez-Reyes, “The role of oxidative stress in the development of

alcoholic liver disease,” Rev. Gastroenterol. México (English Ed., vol. 79, no. 2, pp. 135–144, 2014.

S. D. Shukla and R. W. Lim, “Epigenetic effects of ethanol on the liver and gastrointestinal

system,” Alcohol Res. Curr. Rev., vol. 35, no. 1, p. 47, 2013.

F. A. R. Lívero and A. Acco, “Molecular basis of alcoholic fatty liver disease: From incidence to

treatment,” Hepatol. Res., vol. 46, no. 1, pp. 111–123, 2016.

T. Jiang, G. Zhang, and Z. Lou, “Role of the sterol regulatory element binding protein pathway

in tumorigenesis,” Front. Oncol., vol. 10, p. 1788, 2020.

X. Cheng, J. Li, and D. Guo, “SCAP/SREBPs are central players in lipid metabolism and novel

metabolic targets in cancer therapy,” Curr. Top. Med. Chem., vol. 18, no. 6, pp. 484–493, 2018.

R. A. DeBose-Boyd and J. Ye, “SREBPs in lipid metabolism, insulin signaling, and beyond,”

Trends Biochem. Sci., vol. 43, no. 5, pp. 358–368, 2018.

H. Shimano, “SREBP-1c and TFE3, energy transcription factors that regulate hepatic insulin

signaling,” J. Mol. Med., vol. 85, pp. 437–444, 2007.

J. T. Nickels, “New links between lipid accumulation and cancer progression,” J. Biol. Chem.,

vol. 293, no. 17, pp. 6635–6636, 2018.

J. Yang and M. S. Stack, “Lipid regulatory proteins as potential therapeutic targets for ovarian

cancer in obese women,” Cancers (Basel)., vol. 12, no. 11, p. 3469, 2020.

K. J. Jeong et al., “Progesterone increases hepatic lipid content and plasma lipid levels through

PR-B-mediated lipogenesis,” Biomed. Pharmacother., vol. 172, p. 116281, 2024.

Q. Long, H. Chen, W. Yang, L. Yang, and L. Zhang, “Delphinidin-3-sambubioside from

Hibiscus sabdariffa. L attenuates hyperlipidemia in high fat diet-induced obese rats and oleic acidinduced steatosis in HepG2 cells,” Bioengineered, vol. 12, no. 1, pp. 3837–3849, 2021.

S. Deng, B. Chen, J. Huo, and X. Liu, “Therapeutic potential of NR4A1 in cancer: Focus on

metabolism,” Front. Oncol., vol. 12, p. 972984, 2022.

Y. Huang, Y. F. Wang, X. Z. Ruan, C. W. Lau, L. Wang, and Y. Huang, “The role of KLF2 in

regulating hepatic lipogenesis and blood cholesterol homeostasis via the SCAP/SREBP pathway,” J.

Lipid Res., vol. 65, no. 1, 2024.

Y. Fan et al., “STAT3 activation of SCAP-SREBP-1 signaling upregulates fatty acid synthesis to

promote tumor growth,” J. Biol. Chem., p. 107351, 2024.

Y. Zhang et al., “Nuclear factor Y participates in alcoholic liver disease by activating SREBP1

expression in mice,” Biochem. Biophys. Res. Commun., vol. 541, pp. 90–94, 2021.

H. K. Seitz et al., “Alcoholic liver disease,” Nat. Rev. Dis. Prim., vol. 4, no. 1, p. 16, 2018.

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X. Xu, J.-S. So, J.-G. Park, and A.-H. Lee, “Transcriptional control of hepatic lipid metabolism

by SREBP and ChREBP,” in Seminars in liver disease, 2013, vol. 33, no. 04, pp. 301–311.

A. G. Linden et al., “Interplay between ChREBP and SREBP-1c coordinates postprandial

glycolysis and lipogenesis in livers of mice [S],” J. Lipid Res., vol. 59, no. 3, pp. 475–487, 2018.

R.-B. Ding, J. Bao, and C.-X. Deng, “Emerging roles of SIRT1 in fatty liver diseases,” Int. J.

Biol. Sci., vol. 13, no. 7, p. 852, 2017.

J. García-Villafranca, A. Guillén, and J. Castro, “Ethanol consumption impairs regulation of fatty

acid metabolism by decreasing the activity of AMP-activated protein kinase in rat liver,” Biochimie,

vol. 90, no. 3, pp. 460–466, 2008.

A. Oliveros-Montiel, G. Santos-López, and V. Sedeño-Monge, “Proteins involved in lipid

metabolism as possible biomarkers or predisposing factors for non-alcoholic fatty liver disease,” Acta

Gastroenterol. Belg., vol. 83, no. 4, pp. 622–630, 2020.

H. Shimano, “SREBPs: physiology and pathophysiology of the SREBP family,” FEBS J., vol.

, no. 3, pp. 616–621, 2009.

J. D. Horton, J. L. Goldstein, and M. S. Brown, “SREBPs: activators of the complete program of

cholesterol and fatty acid synthesis in the liver,” J. Clin. Invest., vol. 109, no. 9, pp. 1125–1131, 2002.

W. Jeong et al., “Paracrine activation of hepatic CB1 receptors by stellate cell-derived

endocannabinoids mediates alcoholic fatty liver,” Cell Metab., vol. 7, no. 3, pp. 227–235, 2008

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2024-10-21

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