Incretins and MASLD: at the Crossroads of Endocrine and Hepatic Disorders

World Health Organization. Obesity and overweight n.d. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 2025

Vassallo P, Driver SL, Stone NJ. Metabolic Syndrome: An Evolving Clinical Construct. Prog Cardiovasc Dis. 2016;59:172–7. https://doi.org/10.1016/j.pcad.2016.07.012.

Article  PubMed  Google Scholar 

Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78:1966. https://doi.org/10.1097/HEP.0000000000000520.

Article  PubMed  Google Scholar 

Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022;7:851–61. https://doi.org/10.1016/S2468-1253(22)00165-0.

Article  PubMed  CAS  Google Scholar 

Younossi ZM, Kalligeros M, Henry L. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2024;31:S32-50. https://doi.org/10.3350/cmh.2024.0431.

Article  PubMed  PubMed Central  Google Scholar 

Lonardo A, Mantovani A, Lugari S, Targher G. Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity. Ann Hepatol. 2020;19:359–66. https://doi.org/10.1016/j.aohep.2020.03.001.

Article  PubMed  CAS  Google Scholar 

Le Garf S, Nègre V, Anty R, Gual P. Metabolic fatty liver disease in children: a growing public health problem. Biomedicines. 2021;9:1915. https://doi.org/10.3390/biomedicines9121915.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Samuel VT, Shulman GI. Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases. Cell Metab. 2018;27:22–41. https://doi.org/10.1016/j.cmet.2017.08.002.

Article  PubMed  CAS  Google Scholar 

Lallukka S, Yki-Järvinen H. Non-alcoholic fatty liver disease and risk of type 2 diabetes. Best Pract Res Clin Endocrinol Metab. 2016;30:385–95. https://doi.org/10.1016/j.beem.2016.06.006.

Article  PubMed  CAS  Google Scholar 

Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363:1341–50. https://doi.org/10.1056/NEJMra0912063.

Article  PubMed  CAS  Google Scholar 

Kucukoglu O, Sowa J-P, Mazzolini GD, Syn W-K, Canbay A. Hepatokines and adipokines in NASH-related hepatocellular carcinoma. J Hepatol. 2021;74:442–57. https://doi.org/10.1016/j.jhep.2020.10.030.

Article  PubMed  CAS  Google Scholar 

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2024 May;74(3):229-63. https://doi.org/10.3322/caac.21834.

Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7:1–28. https://doi.org/10.1038/s41572-020-00240-3.

Article  Google Scholar 

Younossi Z, Stepanova M, Ong JP, Jacobson IM, Bugianesi E, Duseja A, et al. Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol. 2019;17:748-755.e3. https://doi.org/10.1016/j.cgh.2018.05.057.

Article  PubMed  Google Scholar 

Magkos F, Fraterrigo G, Yoshino J, Luecking C, Kirbach K, Kelly SC, et al. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 2016;23:591–601. https://doi.org/10.1016/j.cmet.2016.02.005.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Creutzfeldt W. The incretin concept today. Diabetologia. 1979;16:75–85. https://doi.org/10.1007/BF01225454.

Article  PubMed  CAS  Google Scholar 

Přáda Brichtová E, Krupová M, Bouř P, Lindo V, Gomes dos Santos A, Jackson SE. Glucagon-like peptide 1 aggregates into low-molecular-weight oligomers off-pathway to fibrillation. Biophysical Journal 2023;122:2475–88. https://doi.org/10.1016/j.bpj.2023.04.027.

Gautier J-F, Choukem S-P, Girard J. Physiology of incretins (GIP and GLP-1) and abnormalities in type 2 diabetes. Diabetes Metab. 2008;34:S65-72. https://doi.org/10.1016/S1262-3636(08)73397-4.

Article  PubMed  CAS  Google Scholar 

Liu QK. Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists. Front Endocrinol (Lausanne). 2024;15:1431292. https://doi.org/10.3389/fendo.2024.1431292.

Article  PubMed  Google Scholar 

Son JW, Lim S. Glucagon-like peptide-1 based therapies: a new horizon in obesity management. Endocrinol Metab. 2024;39:206–21. https://doi.org/10.3803/EnM.2024.1940.

Article  CAS  Google Scholar 

Hall S, Isaacs D, Clements JN. Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist. Clin Pharmacokinet. 2018;57:1529–38. https://doi.org/10.1007/s40262-018-0668-z.

Article  PubMed  CAS  Google Scholar 

Petrova L, Andreevska K, Parvova I, Petkova V. Systematic review of the efficacy and safety of GLP-1 receptor agonists in the treatment of patients with type 2 diabetes mellitus. Pharmacia. 2024;71:1–17. https://doi.org/10.3897/pharmacia.71.e132148.

Article  CAS  Google Scholar 

Min T, Bain SC. The role of tirzepatide, dual gip and glp-1 receptor agonist, in the management of type 2 diabetes: the surpass clinical trials. Diabetes Ther. 2021;12:143–57. https://doi.org/10.1007/s13300-020-00981-0.

Article  PubMed  CAS  Google Scholar 

Schneck K, Urva S. Population pharmacokinetics of the GIP/GLP receptor agonist tirzepatide. CPT: Pharmacometrics & Systems Pharmacology. 2024 Mar;13(3):494-503. https://doi.org/10.1002/psp4.13099.

Forzano I, Varzideh F, Avvisato R, Jankauskas SS, Mone P, Santulli G. Tirzepatide: a systematic update. Int J Mol Sci. 2022;23:14631. https://doi.org/10.3390/ijms232314631.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Nauck MA, D‘Alessio DA. Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Cardiovascular Diabetology 2022;21:169. https://doi.org/10.1186/s12933-022-01604-7.

Shilleh AH, Viloria K, Broichhagen J, Campbell JE, Hodson DJ. GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells. Peptides. 2024;175:171179. https://doi.org/10.1016/j.peptides.2024.171179.

Article  PubMed  CAS  Google Scholar 

Farr OM, Sofopoulos M, Tsoukas MA, Dincer F, Thakkar B, Sahin-Efe A, et al. GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial. Diabetologia. 2016;59:954–65. https://doi.org/10.1007/s00125-016-3874-y.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Almutairi M, Al Batran R, Ussher JR. Glucagon-like peptide-1 receptor action in the vasculature. Peptides. 2019;111:26–32. https://doi.org/10.1016/j.peptides.2018.09.002.

Article  PubMed  CAS  Google Scholar 

Grunddal KV, Jensen EP, Ørskov C, Andersen DB, Windeløv JA, Poulsen SS, et al. Expression Profile of the GLP-1 Receptor in the Gastrointestinal Tract and Pancreas in Adult Female Mice. Endocrinology. 2022;163:bqab216. https://doi.org/10.1210/endocr/bqab216.

Article  PubMed  CAS  Google Scholar 

Sato T, Shimizu T, Fujita H, Imai Y, Drucker DJ, Seino Y, et al. GLP-1 Receptor Signaling Differentially Modifies the Outcomes of Sterile vs Viral Pulmonary Inflammation in Male Mice. Endocrinology. 2020;161:bqaa201. https://doi.org/10.1210/endocr/bqaa201.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Adriaenssens A, Broichhagen J, Bray A de, Ast J, Hasib A, Jones B, et al. Hypothalamic and brainstem glucose-dependent insulinotropic polypeptide receptor neurons employ distinct mechanisms to affect feeding. JCI Insight 2023;8. https://doi.org/10.1172/jci.insight.164921.

da Silva LN, Cabaleiro A, Novoa E, Riobello C, Knerr PJ, He Y, et al. GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells. Cell Mol Life Sci. 2024;81:468. https://doi.org/10.1007/s00018-024-05507-6.

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