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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

GLP-1/GLP-1RAs: New Options for the Drug Treatment of NAFLD

Author(s): Haoran Jiang and Linquan Zang*

Volume 30, Issue 2, 2024

Published on: 16 January, 2024

Page: [100 - 114] Pages: 15

DOI: 10.2174/0113816128283153231226103218

Price: $65

Abstract

Non-alcoholic fatty liver disease (NAFLD) has recently emerged as a global public health concern. Currently, the cornerstone of NAFLD treatment is lifestyle modification and, if necessary, weight loss. However, compliance is a challenge, and this approach alone may not be sufficient to halt and treat the more serious disease development, so medication is urgently needed. Nevertheless, no medicines are approved to treat NAFLD. Glucagon-like peptide-1 (GLP-1) is an enteropeptide hormone that inhibits glucagon synthesis, promotes insulin secretion, and delays gastric emptying. GLP-1 has been found in recent studies to be beneficial for the management of NAFLD, and the marketed GLP-1 agonist drugs have different degrees of effectiveness for NAFLD while lowering blood glucose. In this article, we review GLP-1 and its physiological roles, the pathogenesis of NAFLD, the correlation between NAFLD and GLP-1 signaling, and potential strategies for GLP-1 treatment of NAFLD.

Keywords: Glucagon-like peptide-1, glucagon-like peptide-1 receptor agonist, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, insulin resistance, steatosis.

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[1]
European Association for the Study of the L. EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia 2016; 59(6): 1121-40.
[http://dx.doi.org/10.1007/s00125-016-3902-y]
[2]
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the american association for the study of liver diseases. Hepatology 2018; 67(1): 328-57.
[http://dx.doi.org/10.1002/hep.29367] [PMID: 28714183]
[3]
Samuel VT, Shulman GI. Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases. Cell Metab 2018; 27(1): 22-41.
[http://dx.doi.org/10.1016/j.cmet.2017.08.002] [PMID: 28867301]
[4]
Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013; 10(6): 330-44.
[http://dx.doi.org/10.1038/nrgastro.2013.41] [PMID: 23507799]
[5]
Tanaka N, Kimura T, Fujimori N, Nagaya T, Komatsu M, Tanaka E. Current status, problems, and perspectives of non-alcoholic fatty liver disease research. World J Gastroenterol 2019; 25(2): 163-77.
[http://dx.doi.org/10.3748/wjg.v25.i2.163] [PMID: 30670907]
[6]
Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol 2023; 79(6): 1542-56.
[http://dx.doi.org/10.1016/j.jhep.2023.06.003] [PMID: 37364790]
[7]
Chen L, Tao X, Zeng M, Mi Y, Xu L. Clinical and histological features under different nomenclatures of fatty liver disease: NAFLD, MAFLD, MASLD and MetALD. J Hepatol 2023; S0168-8278(23): 05075-4..
[http://dx.doi.org/10.1016/j.jhep.2023.08.021] [PMID: 37714381]
[8]
Song SJ, Lai JCT, Wong GLH, Wong VWS, Yip TCF. Can we use old NAFLD data under the new MASLD definition? J Hepatol 2023; S0168-8278(23): 05000-6.
[http://dx.doi.org/10.1016/j.jhep.2023.07.021] [PMID: 37541393]
[9]
Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018; 15(1): 11-20.
[http://dx.doi.org/10.1038/nrgastro.2017.109] [PMID: 28930295]
[10]
Estes C, Anstee QM, 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 Hepatol 2018; 69(4): 896-904.
[http://dx.doi.org/10.1016/j.jhep.2018.05.036] [PMID: 29886156]
[11]
Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology 2018; 67(1): 123-33.
[http://dx.doi.org/10.1002/hep.29466] [PMID: 28802062]
[12]
Adams LA, Roberts SK, Strasser SI, et al. Nonalcoholic fatty liver disease burden: Australia, 2019–2030. J Gastroenterol Hepatol 2020; 35(9): 1628-35.
[http://dx.doi.org/10.1111/jgh.15009] [PMID: 32048317]
[13]
Winn NC, Liu Y, Rector RS, Parks EJ, Ibdah JA, Kanaley JA. Energy-matched moderate and high intensity exercise training improves nonalcoholic fatty liver disease risk independent of changes in body mass or abdominal adiposity - A randomized trial. Metabolism 2018; 78: 128-40.
[http://dx.doi.org/10.1016/j.metabol.2017.08.012] [PMID: 28941598]
[14]
Yoneda M, Honda Y, Saito S, Nakajima A. What considerations are there for the pharmacotherapeutic management of nonalcoholic steatohepatitis? Expert Opin Pharmacother 2021; 22(10): 1217-20.
[http://dx.doi.org/10.1080/14656566.2021.1912014] [PMID: 33880982]
[15]
Mantovani A, Petracca G, Beatrice G, Csermely A, Lonardo A, Targher G. Glucagon-like peptide-1 receptor agonists for treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An updated meta-analysis of randomized controlled trials. Metabolites 2021; 11(2): 73.
[http://dx.doi.org/10.3390/metabo11020073] [PMID: 33513761]
[16]
Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med 2018; 24(7): 908-22.
[http://dx.doi.org/10.1038/s41591-018-0104-9] [PMID: 29967350]
[17]
Petit JM, Verges B. GLP-1 receptor agonists in NAFLD. Diabetes Metab 2017; 43(S1): 2S28-33.
[18]
Graaf C, Donnelly D, Wootten D, et al. Glucagon-like peptide-1 and its class B G protein-coupled receptors: A long march to therapeutic successes. Pharmacol Rev 2016; 68(4): 954-1013.
[http://dx.doi.org/10.1124/pr.115.011395] [PMID: 27630114]
[19]
Davis EM, Sandoval DA. Glucagon-like peptide-1: Actions and influence on pancreatic hormone function. Compr Physiol 2020; 10(2): 577-95.
[http://dx.doi.org/10.1002/cphy.c190025] [PMID: 32163198]
[20]
Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab 2019; 30: 72-130.
[http://dx.doi.org/10.1016/j.molmet.2019.09.010] [PMID: 31767182]
[21]
Holst JJ, Ørskov C, Vagn Nielsen O, Schwartz TW. Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut. FEBS Lett 1987; 211(2): 169-74.
[http://dx.doi.org/10.1016/0014-5793(87)81430-8] [PMID: 3542566]
[22]
Orskov C, Bersani M, Johnsen AH, Højrup P, Holst JJ. Complete sequences of glucagon-like peptide-1 from human and pig small intestine. J Biol Chem 1989; 264(22): 12826-9.
[http://dx.doi.org/10.1016/S0021-9258(18)51561-1] [PMID: 2753890]
[23]
Ørskov C, Rabenhøj L, Wettergren A, Kofod H, Holst JJ. Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans. Diabetes 1994; 43(4): 535-9.
[http://dx.doi.org/10.2337/diab.43.4.535] [PMID: 8138058]
[24]
Rouillé Y, Martin S, Steiner DF. Differential processing of proglucagon by the subtilisin-like prohormone convertases PC2 and PC3 to generate either glucagon or glucagon-like peptide. J Biol Chem 1995; 270(44): 26488-96.
[http://dx.doi.org/10.1074/jbc.270.44.26488] [PMID: 7592866]
[25]
Mojsov S, Kopczynski MG, Habener JF. Both amidated and nonamidated forms of glucagon-like peptide I are synthesized in the rat intestine and the pancreas. J Biol Chem 1990; 265(14): 8001-8.
[http://dx.doi.org/10.1016/S0021-9258(19)39030-1] [PMID: 1692320]
[26]
Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 1995; 80(3): 952-7.
[PMID: 7883856]
[27]
Mentlein R, Gallwitz B, Schmidt WE. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7–36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 1993; 214(3): 829-35.
[http://dx.doi.org/10.1111/j.1432-1033.1993.tb17986.x] [PMID: 8100523]
[28]
Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 1995; 44(9): 1126-31.
[http://dx.doi.org/10.2337/diab.44.9.1126] [PMID: 7657039]
[29]
Meier JJ, Nauck MA, Kranz D, et al. Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes 2004; 53(3): 654-62.
[http://dx.doi.org/10.2337/diabetes.53.3.654] [PMID: 14988249]
[30]
Kreymann B, Ghatei MA, Williams G, Bloom SR. Glucagon-like peptide-1 7-36: A physiological incretin in man. Lancet 1987; 330(8571): 1300-4.
[http://dx.doi.org/10.1016/S0140-6736(87)91194-9] [PMID: 2890903]
[31]
Vilsbøll T, Krarup T, Madsbad S, Holst JJ. Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept 2003; 114(2-3): 115-21.
[http://dx.doi.org/10.1016/S0167-0115(03)00111-3] [PMID: 12832099]
[32]
Holst JJ. The incretin system in healthy humans: The role of GIP and GLP-1. Metabolism 2019; 96: 46-55.
[http://dx.doi.org/10.1016/j.metabol.2019.04.014] [PMID: 31029770]
[33]
Edwards CM, Todd JF, Mahmoudi M, et al. Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: Studies with the antagonist exendin 9-39. Diabetes 1999; 48(1): 86-93.
[http://dx.doi.org/10.2337/diabetes.48.1.86] [PMID: 9892226]
[34]
De S, Banerjee S, Kumar SKA, Paira P. Critical role of dipeptidyl peptidase IV: A therapeutic target for diabetes and cancer. Mini Rev Med Chem 2018; 19(2): 88-97.
[http://dx.doi.org/10.2174/1389557518666180423112154] [PMID: 29692250]
[35]
Deacon CF. Physiology and pharmacology of DPP-4 in glucose homeostasis and the treatment of type 2 diabetes. Front Endocrinol 2019; 10: 80.
[http://dx.doi.org/10.3389/fendo.2019.00080] [PMID: 30828317]
[36]
Gilbert MP, Pratley RE. GLP-1 analogs and DPP-4 inhibitors in type 2 diabetes therapy: Review of head-to-head clinical trials. Front Endocrinol 2020; 11: 178.
[http://dx.doi.org/10.3389/fendo.2020.00178] [PMID: 32308645]
[37]
Gribble FM, Reimann F. Metabolic messengers: Glucagon-like peptide 1. Nat Metab 2021; 3(2): 142-8.
[http://dx.doi.org/10.1038/s42255-020-00327-x] [PMID: 33432200]
[38]
Maselli DB, Camilleri M. Effects of GLP-1 and its analogs on gastric physiology in diabetes mellitus and obesity. Adv Exp Med Biol 2020; 1307: 171-92.
[http://dx.doi.org/10.1007/5584_2020_496] [PMID: 32077010]
[39]
Rowlands J, Heng J, Newsholme P, Carlessi R. Pleiotropic effects of GLP-1 and analogs on cell signaling, metabolism, and function. Front Endocrinol 2018; 9: 672.
[http://dx.doi.org/10.3389/fendo.2018.00672] [PMID: 30532733]
[40]
Day CP, James OFW. Steatohepatitis: A tale of two “hits”? Gastroenterology 1998; 114(4): 842-5.
[http://dx.doi.org/10.1016/S0016-5085(98)70599-2] [PMID: 9547102]
[41]
Guo X, Yin X, Liu Z, Wang J. Non-Alcoholic Fatty Liver Disease (NAFLD) pathogenesis and natural products for prevention and treatment. Int J Mol Sci 2022; 23(24): 15489.
[http://dx.doi.org/10.3390/ijms232415489] [PMID: 36555127]
[42]
Cobbina E, Akhlaghi F. Non-alcoholic fatty liver disease (NAFLD) - Pathogenesis, classification, and effect on drug metabolizing enzymes and transporters. Drug Metab Rev 2017; 49(2): 197-211.
[http://dx.doi.org/10.1080/03602532.2017.1293683] [PMID: 28303724]
[43]
Jou J, Choi S, Diehl A. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis 2008; 28(4): 370-9.
[http://dx.doi.org/10.1055/s-0028-1091981] [PMID: 18956293]
[44]
Pafili K, Roden M. Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans. Mol Metab 2021; 50: 101122.
[http://dx.doi.org/10.1016/j.molmet.2020.101122] [PMID: 33220492]
[45]
Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis. Hepatology 2010; 52(5): 1836-46.
[http://dx.doi.org/10.1002/hep.24001] [PMID: 21038418]
[46]
Makri E, Goulas A, Polyzos SA. Epidemiology, pathogenesis, diagnosis and emerging treatment of nonalcoholic fatty liver disease. Arch Med Res 2021; 52(1): 25-37.
[http://dx.doi.org/10.1016/j.arcmed.2020.11.010] [PMID: 33334622]
[47]
Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 2016; 65(8): 1038-48.
[http://dx.doi.org/10.1016/j.metabol.2015.12.012] [PMID: 26823198]
[48]
Bessone F, Razori MV, Roma MG. Molecular pathways of nonalcoholic fatty liver disease development and progression. Cell Mol Life Sci 2019; 76(1): 99-128.
[http://dx.doi.org/10.1007/s00018-018-2947-0] [PMID: 30343320]
[49]
Francisco V, Sanz MJ, Real JT, et al. Adipokines in non-alcoholic fatty liver disease: Are we on the road toward new biomarkers and therapeutic targets? Biology 2022; 11(8): 1237.
[http://dx.doi.org/10.3390/biology11081237] [PMID: 36009862]
[50]
Marra F, Svegliati-Baroni G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. J Hepatol 2018; 68(2): 280-95.
[http://dx.doi.org/10.1016/j.jhep.2017.11.014] [PMID: 29154964]
[51]
Apostolopoulou M, Gordillo R, Koliaki C, et al. Specific hepatic sphingolipids relate to insulin resistance, oxidative stress, and inflammation in nonalcoholic steatohepatitis. Diabetes Care 2018; 41(6): 1235-43.
[http://dx.doi.org/10.2337/dc17-1318] [PMID: 29602794]
[52]
Yadav P, Singh SK, Rajput S, et al. Therapeutic potential of stem cells in regeneration of liver in chronic liver diseases: Current perspectives and future challenges. Pharmacol Ther 2024; 253: 108563.
[http://dx.doi.org/10.1016/j.pharmthera.2023.108563] [PMID: 38013053]
[53]
Tilg H, Burcelin R, Tremaroli V. Liver tissue microbiome in NAFLD: Next step in understanding the gut–liver axis? Gut 2020; 69(8): 1373-4.
[http://dx.doi.org/10.1136/gutjnl-2019-320490] [PMID: 32060128]
[54]
Kolodziejczyk AA, Zheng D, Shibolet O, Elinav E. The role of the microbiome in NAFLD and NASH. EMBO Mol Med 2019; 11(2): e9302.
[http://dx.doi.org/10.15252/emmm.201809302] [PMID: 30591521]
[55]
Dongiovanni P, Valenti L, Rametta R, et al. Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease. Gut 2010; 59(2): 267-73.
[http://dx.doi.org/10.1136/gut.2009.190801] [PMID: 20176643]
[56]
Thangapandi VR, Knittelfelder O, Brosch M, et al. Loss of hepatic Mboat7 leads to liver fibrosis. Gut 2021; 70(5): 940-50.
[http://dx.doi.org/10.1136/gutjnl-2020-320853] [PMID: 32591434]
[57]
Metwally M, Bayoumi A, Romero-Gomez M, et al. A polymorphism in the Irisin-encoding gene (FNDC5) associates with hepatic steatosis by differential miRNA binding to the 3′UTR. J Hepatol 2019; 70(3): 494-500.
[http://dx.doi.org/10.1016/j.jhep.2018.10.021] [PMID: 30389552]
[58]
Caputo V, Tarantino G, Santini SJ, Fracassi G, Balsano C. The role of epigenetic control of mitochondrial (dys)function in MASLD onset and progression. Nutrients 2023; 15(22): 4757.
[http://dx.doi.org/10.3390/nu15224757] [PMID: 38004151]
[59]
Pedersen JS, Rygg MO, Serizawa RR, et al. Effects of Roux-en-Y gastric bypass and sleeve gastrectomy on non-alcoholic fatty liver disease: A 12-month follow-up study with paired liver biopsies. J Clin Med 2021; 10(17): 3783.
[http://dx.doi.org/10.3390/jcm10173783] [PMID: 34501231]
[60]
Chen F, Zhou Y, Wu Z, Li Y, Zhou W, Wang Y. Integrated analysis of key genes and pathways involved in nonalcoholic steatohepatitis improvement after Roux-en-Y gastric bypass surgery. Front Endocrinol 2021; 11: 611213.
[http://dx.doi.org/10.3389/fendo.2020.611213] [PMID: 33603714]
[61]
Schneck AS, Anty R, Patouraux S, et al. Roux-en Y gastric bypass results in long-term remission of hepatocyte apoptosis and hepatic histological features of non-alcoholic steatohepatitis. Front Physiol 2016; 7: 344.
[http://dx.doi.org/10.3389/fphys.2016.00344] [PMID: 27594839]
[62]
Cazzo E, Pareja JC, Chaim EA. Nonalcoholic fatty liver disease and bariatric surgery: A comprehensive review. Sao Paulo Med J 2017; 135(3): 277-95.
[http://dx.doi.org/10.1590/1516-3180.2016.0306311216] [PMID: 28562737]
[63]
Bernsmeier C, Meyer-Gerspach AC, Blaser LS, et al. Glucose-induced glucagon-like peptide 1 secretion is deficient in patients with non-alcoholic fatty liver disease. PLoS One 2014; 9(1): e87488.
[http://dx.doi.org/10.1371/journal.pone.0087488] [PMID: 24489924]
[64]
Liu Y, Wei R, Hong TP. Potential roles of glucagon-like peptide-1-based therapies in treating non-alcoholic fatty liver disease. World J Gastroenterol 2014; 20(27): 9090-7.
[PMID: 25083081]
[65]
Miyazaki M, Kato M, Tanaka K, et al. Increased hepatic expression of dipeptidyl peptidase-4 in non-alcoholic fatty liver disease and its association with insulin resistance and glucose metabolism. Mol Med Rep 2012; 5(3): 729-33.
[PMID: 22179204]
[66]
Marušić M, Paić M, Knobloch M, Liberati Pršo AM. NAFLD, insulin resistance, and diabetes mellitus type 2. Can J Gastroenterol Hepatol 2021; 2021: 1-9.
[http://dx.doi.org/10.1155/2021/6613827] [PMID: 33681089]
[67]
Fujii H, Kawada N. Japan study group of Nafld J-N. the role of insulin resistance and diabetes in nonalcoholic fatty liver disease. Int J Mol Sci 2020; 21.
[68]
Lecture BC. Non-alcoholic fatty liver disease, insulin resistance and ectopic fat: A new problem in diabetes management. Diabet Med 2012; 29(9): 1098-107.
[http://dx.doi.org/10.1111/j.1464-5491.2012.03732.x] [PMID: 22672330]
[69]
Zhang C, Zhou B, Sheng J, Chen Y, Cao Y, Chen C. Molecular mechanisms of hepatic insulin resistance in nonalcoholic fatty liver disease and potential treatment strategies. Pharmacol Res 2020; 159: 104984.
[http://dx.doi.org/10.1016/j.phrs.2020.104984] [PMID: 32502637]
[70]
Kitade H, Chen G, Ni Y, Ota T. Nonalcoholic fatty liver disease and insulin resistance: New insights and potential new treatments. Nutrients 2017; 9(4): 387.
[http://dx.doi.org/10.3390/nu9040387] [PMID: 28420094]
[71]
Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: Pathophysiology and clinical implications. Gastroenterology 2012; 142(4): 711-725.e6.
[http://dx.doi.org/10.1053/j.gastro.2012.02.003] [PMID: 22326434]
[72]
Khan RS, Bril F, Cusi K, Newsome PN. Modulation of insulin resistance in nonalcoholic fatty liver disease. Hepatology 2019; 70(2): 711-24.
[http://dx.doi.org/10.1002/hep.30429] [PMID: 30556145]
[73]
Fernandez J, Valdeolmillos M. Glucose-dependent stimulatory effect of glucagon-like peptide 1(7-36) amide on the electrical activity of pancreatic beta-cells recorded in vivo. Diabetes 1999; 48(4): 754-7.
[http://dx.doi.org/10.2337/diabetes.48.4.754] [PMID: 10102691]
[74]
Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci 1987; 84(10): 3434-8.
[http://dx.doi.org/10.1073/pnas.84.10.3434] [PMID: 3033647]
[75]
Holz GG. Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell. Diabetes 2004; 53(1): 5-13.
[http://dx.doi.org/10.2337/diabetes.53.1.5] [PMID: 14693691]
[76]
Béguin P, Nagashima K, Nishimura M, Gonoi T, Seino S. PKA- mediated phosphorylation of the human KATP channel: Separate roles of Kir6.2 and SUR1 subunit phosphorylation. EMBO J 1999; 18(17): 4722-32.
[http://dx.doi.org/10.1093/emboj/18.17.4722] [PMID: 10469651]
[77]
Shigeto M, Cha CY, Rorsman P, Kaku K. A role of PLC/PKC-dependent pathway in GLP-1-stimulated insulin secretion. J Mol Med 2017; 95(4): 361-8.
[http://dx.doi.org/10.1007/s00109-017-1508-6] [PMID: 28097390]
[78]
Shigeto M, Ramracheya R, Tarasov AI, et al. GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation. J Clin Invest 2015; 125(12): 4714-28.
[http://dx.doi.org/10.1172/JCI81975] [PMID: 26571400]
[79]
Dasgupta S, Bhattacharya S, Maitra S, et al. Mechanism of lipid induced insulin resistance: Activated PKCε is a key regulator. Biochim Biophys Acta Mol Basis Dis 2011; 1812(4): 495-506.
[http://dx.doi.org/10.1016/j.bbadis.2011.01.001] [PMID: 21236337]
[80]
Gassaway BM, Petersen MC, Surovtseva YV, et al. PKCε contributes to lipid-induced insulin resistance through cross talk with p70S6K and through previously unknown regulators of insulin signaling. Proc Natl Acad Sci 2018; 115(38): E8996-9005.
[http://dx.doi.org/10.1073/pnas.1804379115] [PMID: 30181290]
[81]
Leong I. Role of PKCε in insulin resistance. Nat Rev Endocrinol 2018; 14(11): 627.
[PMID: 30242279]
[82]
ter Horst KW, Gilijamse PW, Versteeg RI, et al. Hepatic diacylglycerol-associated protein kinase Cε translocation links hepatic steatosis to hepatic insulin resistance in humans. Cell Rep 2017; 19(10): 1997-2004.
[http://dx.doi.org/10.1016/j.celrep.2017.05.035] [PMID: 28591572]
[83]
Gao H, Wang X, Zhang Z, et al. GLP-1 amplifies insulin signaling by up-regulation of IRβ, IRS-1 and Glut4 in 3T3-L1 adipocytes. Endocr J 2007; 32(1): 90-5.
[http://dx.doi.org/10.1007/s12020-007-9011-4] [PMID: 17992607]
[84]
Kawamori D, Shirakawa J, Liew CW, et al. GLP-1 signalling compensates for impaired insulin signalling in regulating beta cell proliferation in βIRKO mice. Diabetologia 2017; 60(8): 1442-53.
[http://dx.doi.org/10.1007/s00125-017-4303-6] [PMID: 28526921]
[85]
Yang H, Wang S, Ye Y, et al. GLP-1 preserves β cell function via improvement on islet insulin signaling in high fat diet feeding mice. Neuropeptides 2021; 85: 102110.
[http://dx.doi.org/10.1016/j.npep.2020.102110] [PMID: 33307381]
[86]
He S, Wu W, Wan Y, et al. GLP-1 receptor activation abrogates β-cell dysfunction by PKA Cα-mediated degradation of thioredoxin interacting protein. Front Pharmacol 2019; 10: 1230.
[http://dx.doi.org/10.3389/fphar.2019.01230] [PMID: 31708773]
[87]
Yaribeygi H, Sathyapalan T, Sahebkar A. Molecular mechanisms by which GLP-1 RA and DPP-4i induce insulin sensitivity. Life Sci 2019; 234: 116776.
[http://dx.doi.org/10.1016/j.lfs.2019.116776] [PMID: 31425698]
[88]
Postic C, Girard J. The role of the lipogenic pathway in the development of hepatic steatosis. Diabetes Metab 2008; 34(6): 643-8.
[http://dx.doi.org/10.1016/S1262-3636(08)74599-3] [PMID: 19195625]
[89]
Armstrong MJ, Hull D, Guo K, et al. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis. J Hepatol 2016; 64(2): 399-408.
[http://dx.doi.org/10.1016/j.jhep.2015.08.038] [PMID: 26394161]
[90]
Lee J, Hong SW, Kim MJ, et al. Dulaglutide ameliorates palmitic acid-induced hepatic steatosis by activating FAM3A signaling pathway. Endocrinol Metab 2022; 37(1): 74-83.
[http://dx.doi.org/10.3803/EnM.2021.1293] [PMID: 35144334]
[91]
Khalifa O, AL-Akl NS, Errafii K, Arredouani A. Exendin-4 alleviates steatosis in an in vitro cell model by lowering FABP1 and FOXA1 expression via the Wnt/-catenin signaling pathway. Sci Rep 2022; 12(1): 2226.
[http://dx.doi.org/10.1038/s41598-022-06143-5] [PMID: 35140289]
[92]
Li L, Zha M, Zhang LY, Wang XF, Zhu ZH, Zou DJ. Glucagon- like peptide-1 regulates lipid metabolism in hepatocytes through Foxo1/3. Zhonghua Nei Ke Za Zhi 2019; 58(1): 39-42.
[PMID: 30605949]
[93]
Parlevliet ET, Wang Y, Geerling JJ, et al. GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice. PLoS One 2012; 7(11): e49152.
[http://dx.doi.org/10.1371/journal.pone.0049152] [PMID: 23133675]
[94]
Gao Z, Song GY, Ren LP, Ma HJ, Ma BQ, Chen SC. β-catenin mediates the effect of GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose diet. Eur J Histochem 2020; 64(3): 64.
[http://dx.doi.org/10.4081/ejh.2020.3160] [PMID: 32930541]
[95]
Fang C, Pan J, Qu N, et al. The AMPK pathway in fatty liver disease. Front Physiol 2022; 13: 970292.
[http://dx.doi.org/10.3389/fphys.2022.970292] [PMID: 36203933]
[96]
Smith BK, Marcinko K, Desjardins EM, Lally JS, Ford RJ, Steinberg GR. Treatment of nonalcoholic fatty liver disease: Role of AMPK. Am J Physiol Endocrinol Metab 2016; 311(4): E730-40.
[http://dx.doi.org/10.1152/ajpendo.00225.2016] [PMID: 27577854]
[97]
Zhou R, Lin C, Cheng Y, et al. Liraglutide alleviates hepatic steatosis and liver injury in T2MD rats via a GLP-1R dependent AMPK pathway. Front Pharmacol 2021; 11: 600175.
[http://dx.doi.org/10.3389/fphar.2020.600175] [PMID: 33746742]
[98]
He Q, Sha S, Sun L, Zhang J, Dong M. GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway. Biochem Biophys Res Commun 2016; 476(4): 196-203.
[http://dx.doi.org/10.1016/j.bbrc.2016.05.086] [PMID: 27208776]
[99]
Xu F, Gao Z, Zhang J, et al. Lack of SIRT1 (Mammalian Sirtuin 1) activity leads to liver steatosis in the SIRT1+/- mice: A role of lipid mobilization and inflammation. Endocrinology 2010; 151(6): 2504-14.
[http://dx.doi.org/10.1210/en.2009-1013] [PMID: 20339025]
[100]
Xu F, Li Z, Zheng X, et al. SIRT1 mediates the effect of GLP-1 receptor agonist exenatide on ameliorating hepatic steatosis. Diabetes 2014; 63(11): 3637-46.
[http://dx.doi.org/10.2337/db14-0263] [PMID: 24947350]
[101]
Fang QH, Shen QL, Li JJ, et al. Inhibition of microRNA-124a attenuates non-alcoholic fatty liver disease through upregulation of adipose triglyceride lipase and the effect of liraglutide intervention. Hepatol Res 2019; 49(7): 743-57.
[http://dx.doi.org/10.1111/hepr.13330] [PMID: 30861258]
[102]
Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab 2009; 9(4): 327-38.
[http://dx.doi.org/10.1016/j.cmet.2009.02.006] [PMID: 19356714]
[103]
Francque S, Szabo G, Abdelmalek MF, et al. Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors. Nat Rev Gastroenterol Hepatol 2021; 18(1): 24-39.
[http://dx.doi.org/10.1038/s41575-020-00366-5] [PMID: 33093663]
[104]
Kersten S, Stienstra R. The role and regulation of the peroxisome proliferator activated receptor alpha in human liver. Biochimie 2017; 136: 75-84.
[http://dx.doi.org/10.1016/j.biochi.2016.12.019] [PMID: 28077274]
[105]
Rakhshandehroo M, Hooiveld G, Müller M, Kersten S. Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human. PLoS One 2009; 4(8): e6796.
[http://dx.doi.org/10.1371/journal.pone.0006796] [PMID: 19710929]
[106]
Francque S, Verrijken A, Caron S, et al. PPARα gene expression correlates with severity and histological treatment response in patients with non-alcoholic steatohepatitis. J Hepatol 2015; 63(1): 164-73.
[http://dx.doi.org/10.1016/j.jhep.2015.02.019] [PMID: 25703085]
[107]
Svegliati-Baroni G, Saccomanno S, Rychlicki C, et al. Glucagon- like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high- fat diet in nonalcoholic steatohepatitis. Liver Int 2011; 31(9): 1285-97.
[http://dx.doi.org/10.1111/j.1478-3231.2011.02462.x] [PMID: 21745271]
[108]
Wang H, Wang L, Li Y, et al. The HIF-2α/PPARα pathway is essential for liraglutide-alleviated, lipid-induced hepatic steatosis. Biomed Pharmacother 2021; 140: 111778.
[http://dx.doi.org/10.1016/j.biopha.2021.111778] [PMID: 34062416]
[109]
Ruscica M, Busnelli M, Runfola E, Corsini A, Sirtori CR. Impact of PPAR-alpha polymorphisms-the case of metabolic disorders and atherosclerosis. Int J Mol Sci 2019; 20(18): 4378.
[http://dx.doi.org/10.3390/ijms20184378] [PMID: 31489930]
[110]
Silva-Veiga FM, Miranda CS, Vasques-Monteiro IML, et al. Peroxisome proliferator-activated receptor-alpha activation and dipeptidyl peptidase-4 inhibition target dysbiosis to treat fatty liver in obese mice. World J Gastroenterol 2022; 28(17): 1814-29.
[http://dx.doi.org/10.3748/wjg.v28.i17.1814] [PMID: 35633911]
[111]
Staiger H, Keuper M, Berti L, Hrabě de Angelis M, Häring HU. Fibroblast growth factor 21-metabolic role in mice and men. Endocr Rev 2017; 38(5): 468-88.
[http://dx.doi.org/10.1210/er.2017-00016] [PMID: 28938407]
[112]
Liu J, Yang K, Yang J, et al. Liver-derived fibroblast growth factor 21 mediates effects of glucagon-like peptide-1 in attenuating hepatic glucose output. EBioMedicine 2019; 41: 73-84.
[http://dx.doi.org/10.1016/j.ebiom.2019.02.037] [PMID: 30827929]
[113]
Yang M, Zhang L, Wang C, et al. Liraglutide increases FGF-21 activity and insulin sensitivity in high fat diet and adiponectin knockdown induced insulin resistance. PLoS One 2012; 7(11): e48392.
[http://dx.doi.org/10.1371/journal.pone.0048392] [PMID: 23152772]
[114]
Liu D, Pang J, Shao W, et al. Hepatic fibroblast growth factor 21 Is involved in mediating functions of liraglutide in mice with dietary challenge. Hepatology 2021; 74(4): 2154-69.
[http://dx.doi.org/10.1002/hep.31856] [PMID: 33851458]
[115]
Yadav P, Khurana A, Bhatti JS, Weiskirchen R, Navik U. Glucagon-like peptide 1 and fibroblast growth factor-21 in non-alcoholic steatohepatitis: An experimental to clinical perspective. Pharmacol Res 2022; 184: 106426.
[http://dx.doi.org/10.1016/j.phrs.2022.106426] [PMID: 36075510]
[116]
Pan Q, Lin S, Li Y, et al. A novel GLP-1 and FGF21 dual agonist has therapeutic potential for diabetes and non-alcoholic steatohepatitis. EBioMedicine 2021; 63: 103202.
[http://dx.doi.org/10.1016/j.ebiom.2020.103202] [PMID: 33421947]
[117]
Zhou M, Mok MTS, Sun H, et al. The anti-diabetic drug exenatide, a glucagon-like peptide-1 receptor agonist, counteracts hepatocarcinogenesis through cAMP-PKA-EGFR-STAT3 axis. Oncogene 2017; 36(29): 4135-49.
[http://dx.doi.org/10.1038/onc.2017.38] [PMID: 28319060]
[118]
Chen H, Shen F, Sherban A, et al. DEP domain-containing mTOR-interacting protein suppresses lipogenesis and ameliorates hepatic steatosis and acute-on-chronic liver injury in alcoholic liver disease. Hepatology 2018; 68(2): 496-514.
[http://dx.doi.org/10.1002/hep.29849] [PMID: 29457836]
[119]
Allaire M, Rautou PE, Codogno P, Lotersztajn S. Autophagy in liver diseases: Time for translation? J Hepatol 2019; 70(5): 985-98.
[http://dx.doi.org/10.1016/j.jhep.2019.01.026] [PMID: 30711404]
[120]
Khawar MB, Gao H, Li W. Autophagy and lipid metabolism. Adv Exp Med Biol 2019; 1206: 359-74.
[http://dx.doi.org/10.1007/978-981-15-0602-4_17] [PMID: 31776994]
[121]
Singh R, Kaushik S, Wang Y, et al. Autophagy regulates lipid metabolism. Nature 2009; 458(7242): 1131-5.
[http://dx.doi.org/10.1038/nature07976] [PMID: 19339967]
[122]
He Y, Ao N, Yang J, Wang X, Jin S, Du J. The preventive effect of liraglutide on the lipotoxic liver injury via increasing autophagy. Ann Hepatol 2020; 19(1): 44-52.
[http://dx.doi.org/10.1016/j.aohep.2019.06.023] [PMID: 31787541]
[123]
Zhang Q, Liu Q, Niu CY. Liraglutide alleviates lipotoxic liver cell damage and promotes autophagy to improve non-alcoholic fatty liver. Zhonghua Gan Zang Bing Za Zhi 2021; 29(5): 456-61.
[PMID: 34107584]
[124]
Fang Y, Ji L, Zhu C, et al. Liraglutide alleviates hepatic steatosis by activating the TFEB-regulated autophagy-lysosomal pathway. Front Cell Dev Biol 2020; 8: 602574.
[http://dx.doi.org/10.3389/fcell.2020.602574] [PMID: 33330497]
[125]
Bhattarai KR, Chaudhary M, Kim HR, Chae HJ. Endoplasmic Reticulum (ER) stress response failure in diseases. Trends Cell Biol 2020; 30(9): 672-5.
[http://dx.doi.org/10.1016/j.tcb.2020.05.004] [PMID: 32561138]
[126]
Marciniak SJ, Chambers JE, Ron D. Pharmacological targeting of endoplasmic reticulum stress in disease. Nat Rev Drug Discov 2022; 21(2): 115-40.
[http://dx.doi.org/10.1038/s41573-021-00320-3] [PMID: 34702991]
[127]
Lemmer IL, Willemsen N, Hilal N, Bartelt A. A guide to understanding endoplasmic reticulum stress in metabolic disorders. Mol Metab 2021; 47: 101169.
[http://dx.doi.org/10.1016/j.molmet.2021.101169] [PMID: 33484951]
[128]
Ajoolabady A, Kaplowitz N, Lebeaupin C, et al. Endoplasmic reticulum stress in liver diseases. Hepatology 2023; 77(2): 619-39.
[http://dx.doi.org/10.1002/hep.32562] [PMID: 35524448]
[129]
Shrestha N, De Franco E, Arvan P, Cnop M. Pathological beta- cell endoplasmic reticulum stress in type 2 diabetes: Current evidence. Front Endocrinol 2021; 12: 650158.
[http://dx.doi.org/10.3389/fendo.2021.650158] [PMID: 33967960]
[130]
Koo JH, Han CY. Signaling nodes associated with endoplasmic reticulum stress during NAFLD progression. Biomolecules 2021; 11(2): 242.
[http://dx.doi.org/10.3390/biom11020242] [PMID: 33567666]
[131]
Cheng CK, Luo JY, Lau CW, et al. A GLP-1 analog lowers ER stress and enhances protein folding to ameliorate homocysteine-induced endothelial dysfunction. Acta Pharmacol Sin 2021; 42(10): 1598-609.
[http://dx.doi.org/10.1038/s41401-020-00589-x] [PMID: 33495519]
[132]
Martins FF, Marinho TS, Cardoso LEM, et al. Semaglutide (GLP-1 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice. Cell Biochem Funct 2022; 40(8): 903-13.
[http://dx.doi.org/10.1002/cbf.3751] [PMID: 36169111]
[133]
Yusta B, Baggio LL, Estall JL, et al. GLP-1 receptor activation improves β cell function and survival following induction of endoplasmic reticulum stress. Cell Metab 2006; 4(5): 391-406.
[http://dx.doi.org/10.1016/j.cmet.2006.10.001] [PMID: 17084712]
[134]
Oh YS, Lee YJ, Kang Y, Han J, Lim OK, Jun HS. Exendin-4 inhibits glucolipotoxic ER stress in pancreatic β cells via regulation of SREBP1c and C/EBPβ transcription factors. J Endocrinol 2013; 216(3): 343-52.
[http://dx.doi.org/10.1530/JOE-12-0311] [PMID: 23257266]
[135]
Sharma S, Mells JE, Fu PP, Saxena NK, Anania FA. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy. PLoS One 2011; 6(9): e25269.
[http://dx.doi.org/10.1371/journal.pone.0025269] [PMID: 21957486]
[136]
Ao N, Yang J, Wang X, Du J. Glucagon-like peptide-1 preserves non-alcoholic fatty liver disease through inhibition of the endoplasmic reticulum stress-associated pathway. Hepatol Res 2016; 46(4): 343-53.
[http://dx.doi.org/10.1111/hepr.12551] [PMID: 26147696]
[137]
Zheng X, Xu F, Liang H, et al. SIRT1/HSF1/HSP pathway is essential for exenatide-alleviated, lipid-induced hepatic endoplasmic reticulum stress. Hepatology 2017; 66(3): 809-24.
[http://dx.doi.org/10.1002/hep.29238] [PMID: 28439947]
[138]
Jiang Y, Wang Z, Ma B, et al. GLP-1 improves adipocyte insulin sensitivity following induction of endoplasmic reticulum stress. Front Pharmacol 2018; 9: 1168.
[http://dx.doi.org/10.3389/fphar.2018.01168] [PMID: 30459598]
[139]
Shiraishi D, Fujiwara Y, Komohara Y, Mizuta H, Takeya M. Glucagon-like peptide-1 (GLP-1) induces M2 polarization of human macrophages via STAT3 activation. Biochem Biophys Res Commun 2012; 425(2): 304-8.
[http://dx.doi.org/10.1016/j.bbrc.2012.07.086] [PMID: 22842565]
[140]
Wang Y, Parlevliet ET, Geerling JJ, et al. Exendin-4 decreases liver inflammation and atherosclerosis development simultaneously by reducing macrophage infiltration. Br J Pharmacol 2014; 171(3): 723-34.
[http://dx.doi.org/10.1111/bph.12490] [PMID: 24490861]
[141]
Eguchi Y, Kitajima Y, Hyogo H, et al. Pilot study of liraglutide effects in non-alcoholic steatohepatitis and non-alcoholic fatty liver disease with glucose intolerance in J apanese patients (LEAN-J). Hepatol Res 2015; 45(3): 269-78.
[http://dx.doi.org/10.1111/hepr.12351] [PMID: 24796231]
[142]
Chen Z, Tian R, She Z, Cai J, Li H. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic Biol Med 2020; 152: 116-41.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.02.025] [PMID: 32156524]
[143]
Ashraf NU, Sheikh TA. Endoplasmic reticulum stress and oxidative stress in the pathogenesis of non-alcoholic fatty liver disease. Free Radic Res 2015; 49(12): 1405-18.
[http://dx.doi.org/10.3109/10715762.2015.1078461] [PMID: 26223319]
[144]
Oh Y, Jun HS. Effects of glucagon-like peptide-1 on oxidative stress and Nrf2 signaling. Int J Mol Sci 2017; 19(1): 26.
[http://dx.doi.org/10.3390/ijms19010026] [PMID: 29271910]
[145]
Wang X, Ao N, Du J, Yang J, Xu J. [Influence of GLP-1 on oxidative stress injury in non-alcoholic fatty liver disease rats]. Zhonghua Gan Zang Bing Za Zhi 2014; 22(10): 757-62.
[PMID: 25496866]
[146]
Yamamoto T, Nakade Y, Yamauchi T, et al. Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice. World J Gastroenterol 2016; 22(8): 2512-23.
[http://dx.doi.org/10.3748/wjg.v22.i8.2512] [PMID: 26937139]
[147]
Li S, Wang X, Zhang J, et al. Exenatide ameliorates hepatic steatosis and attenuates fat mass and FTO gene expression through PI3K signaling pathway in nonalcoholic fatty liver disease. Braz J Med Biol Res 2018; 51(8): e7299.
[http://dx.doi.org/10.1590/1414-431x20187299] [PMID: 29924135]
[148]
Zhu C, Luo Y, Wang H, et al. Liraglutide ameliorates lipotoxicity-induced oxidative stress by activating the nrf2 pathway in hepG2 cells. Horm Metab Res 2020; 52(7): 532-9.
[http://dx.doi.org/10.1055/a-1157-0166] [PMID: 32375182]
[149]
Han X, Ding C, Zhang G, et al. Liraglutide ameliorates obesity-related nonalcoholic fatty liver disease by regulating Sestrin2-mediated Nrf2/HO-1 pathway. Biochem Biophys Res Commun 2020; 525(4): 895-901.
[http://dx.doi.org/10.1016/j.bbrc.2020.03.032] [PMID: 32171530]
[150]
Tong W, Ju L, Qiu M, et al. Liraglutide ameliorates non-alcoholic fatty liver disease by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3–FOXO3a pathway. Hepatol Res 2016; 46(9): 933-43.
[http://dx.doi.org/10.1111/hepr.12634] [PMID: 26666995]
[151]
Safari Z, Gérard P. The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci 2019; 76(8): 1541-58.
[http://dx.doi.org/10.1007/s00018-019-03011-w] [PMID: 30683985]
[152]
Jayachandran M, Qu S. Non-alcoholic fatty liver disease and gut microbial dysbiosis-underlying mechanisms and gut microbiota mediated treatment strategies. Rev Endocr Metab Disord 2023; 24(6): 1189-204.
[http://dx.doi.org/10.1007/s11154-023-09843-z] [PMID: 37840104]
[153]
Geng J, Ni Q, Sun W, Li L, Feng X. The links between gut microbiota and obesity and obesity related diseases. Biomed Pharmacother 2022; 147: 112678.
[http://dx.doi.org/10.1016/j.biopha.2022.112678] [PMID: 35134709]
[154]
Abdalqadir N, Adeli K. GLP-1 and GLP-2 orchestrate intestine integrity, gut microbiota, and immune system crosstalk. Microorganisms 2022; 10(10): 2061.
[http://dx.doi.org/10.3390/microorganisms10102061] [PMID: 36296337]
[155]
Madsen MSA, Holm JB, Pallejà A, et al. Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice. Sci Rep 2019; 9(1): 15582.
[http://dx.doi.org/10.1038/s41598-019-52103-x] [PMID: 31666597]
[156]
Aron-Wisnewsky J, Vigliotti C, Witjes J, et al. Gut microbiota and human NAFLD: Disentangling microbial signatures from metabolic disorders. Nat Rev Gastroenterol Hepatol 2020; 17(5): 279-97.
[http://dx.doi.org/10.1038/s41575-020-0269-9] [PMID: 32152478]
[157]
Leung C, Rivera L, Furness JB, Angus PW. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol 2016; 13(7): 412-25.
[http://dx.doi.org/10.1038/nrgastro.2016.85] [PMID: 27273168]
[158]
Zhang Q, Xiao X, Zheng J, et al. Featured article: Structure moderation of gut microbiota in liraglutide-treated diabetic male rats. Exp Biol Med 2018; 243(1): 34-44.
[http://dx.doi.org/10.1177/1535370217743765] [PMID: 29171288]
[159]
Zhao L, Chen Y, Xia F, et al. A glucagon-like Peptide-1 receptor agonist lowers weight by modulating the structure of gut microbiota. Front Endocrinol 2018; 9: 233.
[http://dx.doi.org/10.3389/fendo.2018.00233] [PMID: 29867765]
[160]
Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci 2013; 110(22): 9066-71.
[http://dx.doi.org/10.1073/pnas.1219451110] [PMID: 23671105]
[161]
Han Y, Li L, Wang B. Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: Current knowledge and perspectives. Front Med 2022; 16(5): 667-85.
[http://dx.doi.org/10.1007/s11684-022-0960-z] [PMID: 36318353]
[162]
Liu Q, Cai B, Zhu L, et al. Liraglutide modulates gut microbiome and attenuates nonalcoholic fatty liver in db/db mice. Life Sci 2020; 261: 118457.
[http://dx.doi.org/10.1016/j.lfs.2020.118457] [PMID: 32961235]
[163]
Moreira GV, Azevedo FF, Ribeiro LM, et al. Liraglutide modulates gut microbiota and reduces NAFLD in obese mice. J Nutr Biochem 2018; 62: 143-54.
[http://dx.doi.org/10.1016/j.jnutbio.2018.07.009] [PMID: 30292107]
[164]
Zhang N, Tao J, Gao L, et al. Liraglutide attenuates nonalcoholic fatty liver disease by modulating gut microbiota in rats administered a high-fat diet. BioMed Res Int 2020; 2020: 1-10.
[http://dx.doi.org/10.1155/2020/2947549] [PMID: 32149099]
[165]
Wang Y, Gao X, Zhang X, et al. Gut microbiota dysbiosis is associated with altered bile acid metabolism in infantile cholestasis. MSystems 2019; 4(6): e00463-19.
[http://dx.doi.org/10.1128/mSystems.00463-19] [PMID: 31848302]
[166]
Liang L, Rao E, Zhang X, et al. GLP-1 receptor agonists modulate blood glucose levels in T2DM by affecting Faecalibacterium prausnitzii abundance in the intestine. Medicine 2023; 102(35): e34978.
[http://dx.doi.org/10.1097/MD.0000000000034978] [PMID: 37657059]
[167]
Siegel EG, Seidenstücker A, Gallwitz B, et al. Insulin secretion defects in liver cirrhosis can be reversed by glucagon-like peptide-1. J Endocrinol 2000; 164(1): 13-9.
[http://dx.doi.org/10.1677/joe.0.1640013] [PMID: 10607933]
[168]
Nouri-Vaskeh M, Khalili N, Khalaji A, et al. Circulating glucagon-like peptide-1 level in patients with liver cirrhosis. Arch Physiol Biochem 2023; 129(2): 373-8.
[http://dx.doi.org/10.1080/13813455.2020.1828479] [PMID: 33043692]
[169]
Yang CT, Yao WY, Yang CY, Peng ZY, Ou HT, Kuo S. Lower risks of cirrhosis and hepatocellular carcinoma with GLP-1RAs in type 2 diabetes: A nationwide cohort study using target trial emulation framework. J Intern Med 2023; 13751.
[http://dx.doi.org/10.1111/joim.13751] [PMID: 37994187]
[170]
Yen FS, Hou MC, Cheng-Chung Wei J, et al. Glucagon-like peptide-1 receptor agonist use in patients with liver cirrhosis and type 2 diabetes. Clin Gastroenterol Hepatol 2023; 2.
[http://dx.doi.org/10.1016/j.cgh.2023.06.004] [PMID: 37331413]
[171]
Huynh D, Renelus BD, Jamorabo DS. Dual metformin and glucagon-like peptide-1 receptor agonist therapy reduces mortality and hepatic complications in cirrhotic patients with diabetes mellitus. Ann Gastroenterol 2023; 36(5): 555-63.
[http://dx.doi.org/10.20524/aog.2023.0814] [PMID: 37664227]
[172]
Kojima M, Takahashi H, Kuwashiro T, et al. Glucagon-like peptide-1 receptor agonist prevented the progression of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis. Int J Mol Sci 2020; 21(16): 5722.
[http://dx.doi.org/10.3390/ijms21165722] [PMID: 32785012]
[173]
Li Q, Xue AY, Li ZL, Yin Z. Liraglutide promotes apoptosis of HepG2 cells by activating JNK signaling pathway. Eur Rev Med Pharmacol Sci 2019; 23(8): 3520-6.
[PMID: 31081108]
[174]
Yamada N, Matsushima-Nishiwaki R, Kobayashi K, Tachi J, Kozawa O. GLP-1 reduces the migration of hepatocellular carcinoma cells via suppression of the stress-activated protein kinase/c-Jun N-terminal kinase pathway. Arch Biochem Biophys 2021; 703: 108851.
[http://dx.doi.org/10.1016/j.abb.2021.108851] [PMID: 33771507]
[175]
Lu X, Xu C, Dong J, et al. Liraglutide activates nature killer cell- mediated antitumor responses by inhibiting IL-6/STAT3 signaling in hepatocellular carcinoma. Transl Oncol 2021; 14(1): 100872.
[http://dx.doi.org/10.1016/j.tranon.2020.100872] [PMID: 32979685]
[176]
Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): A multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 2016; 387(10019): 679-90.
[http://dx.doi.org/10.1016/S0140-6736(15)00803-X] [PMID: 26608256]
[177]
Baggio LL, Drucker DJ. Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. Mol Metab 2021; 46: 101090.
[http://dx.doi.org/10.1016/j.molmet.2020.101090] [PMID: 32987188]

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