MASH as a network disease: therapeutic modulation of interorgan immunometabolic architecture

Javier Crespo , Carolina Jiménez-González , Paula Iruzubieta

Metabolism and Target Organ Damage ›› 2026, Vol. 6 ›› Issue (3) : 39

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Metabolism and Target Organ Damage ›› 2026, Vol. 6 ›› Issue (3) :39 DOI: 10.20517/mtod.2026.54
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MASH as a network disease: therapeutic modulation of interorgan immunometabolic architecture
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Javier Crespo, Carolina Jiménez-González, Paula Iruzubieta. MASH as a network disease: therapeutic modulation of interorgan immunometabolic architecture. Metabolism and Target Organ Damage, 2026, 6 (3) : 39 DOI:10.20517/mtod.2026.54

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References

[1]

Jara M,Norlin J,Kjær MS.et al. Modulation of metabolic, inflammatory and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis Nat Med 2025 31 3128 40 PMC12443624

[2]

Younossi ZM,Koenig AB,Abdelatif D,Fazel Y,Henry L,Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes Hepatology 2016 64 73 84

[3]

Mantovani A,Byrne CD,Bonora E,Targher G. Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis Diabetes Care 2018 41 372 82

[4]

Targher G,Tilg H,Byrne CD. Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach Lancet Gastroenterol Hepatol 2021 6 578 88

[5]

Targher G,Byrne CD,Tilg H. NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications Gut 2020 69 1691 705

[6]

Tacke F, Horn P, Wong VW-S, et al. Publisher correction: EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD): executive summary Diabetologia 2024 67 2608 PMC11519244

[7]

Lazarus JV,Pessoa MG,Shawcross DL,Schwarz P,Su GL,Barquera S. Name MASLD/MASH - and act on it JHEP Rep 2026 8 101674 PMC12919265

[8]

Crespo J,Iruzubieta P,Fernández Rodríguez CM. The liver as a thermometer of cardiometabolic health: time to prioritize MASLD in global health policy Rev Esp Enferm Dig 2025 117 709 11

[9]

Smits MM,Holst JJ. Endogenous glucagon-like peptide (GLP)-1 as alternative for GLP-1 receptor agonists: could this work and how? Diabetes Metab Res Rev 2023;39:e3699

[10]

Kirk RK,Pyke C,von Herrath MG.et al. Immunohistochemical assessment of glucagon-like peptide 1 receptor (GLP-1R) expression in the pancreas of patients with type 2 diabetes Diabetes Obes Metab 2017 19 705 12

[11]

da Silva Lima N,Cabaleiro A,Novoa E.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 PMC11604888

[12]

Tilg H,Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis Hepatology 2010 52 1836 46

[13]

Friedman SL,Neuschwander-Tetri BA,Rinella M,Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies Nat Med 2018 24 908 22 PMC6553468

[14]

Novoa E,Parracho T,Inderhees J.et al. Lack of PCK1 in hepatic stellate cells causes liver fibrosis by fueling tricarboxylic acid cycle and increasing glycolysis Cell Metab 2026 38 729 45.e9

[15]

Ramachandran P,Dobie R,Wilson-Kanamori JR.et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level Nature 2019 575 512 8 PMC6876711

[16]

Saltiel AR,Olefsky JM. Inflammatory mechanisms linking obesity and metabolic disease J Clin Invest 2017 127 1 4 PMC5199709

[17]

Vuppalanchi R,Noureddin M,Alkhouri N,Sanyal AJ. Therapeutic pipeline in nonalcoholic steatohepatitis Nat Rev Gastroenterol Hepatol 2021 18 373 92

[18]

Campbell JE,Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action Cell Metab 2013 17 819 37

[19]

Nauck MA,Tuttle KR,Tschöp MH,Blüher M. Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits Lancet 2026 407 892 908

[20]

Loomba R,Hartman ML,Lawitz EJ.et al. ; SYNERGY-NASH Investigators. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis N Engl J Med 2024 391 299 310

[21]

Marso SP,Daniels GH,Brown-Frandsen K.et al. ; LEADER Steering Committee, LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes N Engl J Med 2016 375 311 22 PMC4985288

[22]

Zhao P,Saltiel AR. From overnutrition to liver injury: AMP-activated protein kinase in nonalcoholic fatty liver diseases J Biol Chem 2020 295 12279 89 PMC7443502

[23]

Petersen KF,Dufour S,Befroy D,Lehrke M,Hendler RE,Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes Diabetes 2005 54 603 8 PMC2995496

[24]

Vilar-Gomez E,Martinez-Perez Y,Calzadilla-Bertot L.et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis Gastroenterology 2015 149 367 78.e5

[25]

Liu X,Zhu L,Liu J,Nie Z,Qiu W. Effect of weight loss interventions on metabolomic signatures in obese children with insulin resistance Amino Acids 2024 56 54 PMC11364699

[26]

Balcázar-Valencia CM,García-Ramos AF,Osorio-Toro LM.et al. Semaglutide effects on metabolic outcomes in diabetes mellitus patients - real world study Diabetes Metab Syndr Obes 2024 17 1667 73 PMC11016261

[27]

Franceschi C,Garagnani P,Parini P,Giuliani C,Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases Nat Rev Endocrinol 2018 14 576 90

[28]

Furman D,Campisi J,Verdin E.et al. Chronic inflammation in the etiology of disease across the life span Nat Med 2019 25 1822 32 PMC7147972

[29]

López-Otín C,Blasco MA,Partridge L,Serrano M,Kroemer G. Hallmarks of aging: an expanding universe Cell 2023 186 243 78

[30]

Pirola CJ,Sookoian S. Epigenetics factors in nonalcoholic fatty liver disease Expert Rev Gastroenterol Hepatol 2022 16 521 36

[31]

Tilg H,Adolph TE,Dudek M,Knolle P. Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity Nat Metab 2021 3 1596 607

[32]

Amjad AI,Sheikh BS,Aslam S. Biological resilience as a crucial determinant in preventing age-associated chronic diseases Front Physiol 2025 16 1741426 PMC12753462

[33]

Le Thuc O,García-Cáceres C. Obesity-induced inflammation: connecting the periphery to the brain Nat Metab 2024 6 1237 52

[34]

Sabbagh MN,Cummings JL,Ballard C.et al. Repurposing glucagon-like peptide-1 receptor agonists for the treatment of neurodegenerative disorders Nat Aging 2026 6 56 67

[35]

Bishehsari F,Post Z,Swanson GR,Keshavarzian A. Circadian rhythms in gastroenterology: the biological clock’s impact on gut health Gastroenterology 2025 169 1380 96

[36]

Tahara Y,Shibata S. Circadian rhythms of liver physiology and disease: experimental and clinical evidence Nat Rev Gastroenterol Hepatol 2016 13 217 26

[37]

Babu AF. Metabolic signatures in lean MASLD: current insights and future directions Metabolites 2025 15 583 PMC12471909

[38]

Sanyal AJ,Brunt EM,Kleiner DE.et al. Endpoints and clinical trial design for nonalcoholic steatohepatitis Hepatology 2011 54 344 53 PMC4014460

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