# Glucagon-like peptide-1 and dual/triple receptor agonists in the treatment of metabolic dysfunction-associated steatotic liver disease: advances in mechanistic research **Authors:** Xinyi Lu, Li Yang PMC · DOI: 10.3389/fmed.2026.1763185 · Frontiers in Medicine · 2026-02-12 ## TL;DR This paper reviews how GLP-1 and related receptor agonists may help treat liver disease linked to metabolic dysfunction. ## Contribution The paper offers new mechanistic insights into how GLP-1 and dual/triple receptor agonists affect MASLD. ## Key findings - GLP-1RAs and dual/triple agonists influence hepatic lipid metabolism. - These agonists modulate inflammatory responses in MASLD. - They may slow fibrosis progression in the liver. ## Abstract Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has emerged as a prevalent and severe global hepatic disorder, necessitating the development of effective therapeutic strategies. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), along with glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG) dual or triple receptor agonists that modulate multiple metabolic pathways, have attracted significant scientific interest due to their multifaceted roles in metabolic regulation. This review provides a comprehensive overview of the mechanistic insights into the effects of GLP-1RAs and dual or triple receptor agonists on the pathophysiology of MASLD, with a focus on hepatic lipid metabolism, inflammatory responses, and fibrosis progression. ## Linked entities - **Proteins:** gcg.S (glucagon S homeolog) - **Diseases:** Metabolic Dysfunction-Associated Steatotic Liver Disease (MONDO:0013209), MASLD (MONDO:0013209) ## Full-text entities - **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, IL22 (interleukin 22) [NCBI Gene 50616] {aka IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, Acta2 (actin alpha 2, smooth muscle, aorta) [NCBI Gene 11475] {aka 0610041G09Rik, Actvs, SMAalpha, SMalphaA, a-SMA, alphaSMA}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, Gcg (glucagon) [NCBI Gene 14526] {aka GLP-1, Glu, PPG}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, SREBF1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 6720] {aka HMD, IFAP2, SREBP1, bHLHd1}, GIP (gastric inhibitory polypeptide) [NCBI Gene 2695], SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, IL18R1 (interleukin 18 receptor 1) [NCBI Gene 8809] {aka CD218a, CDw218a, IL-18R, IL-18R-alpha, IL-18Ralpha, IL-1Rrp}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}, NR1H4 (nuclear receptor subfamily 1 group H member 4) [NCBI Gene 9971] {aka BAR, FXR, HRR-1, HRR1, PFIC5, RIP14}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, THRB (thyroid hormone receptor beta) [NCBI Gene 7068] {aka C-ERBA-2, C-ERBA-BETA, ERBA2, GRTH, NR1A2, PRTH}, Saa2 (serum amyloid A 2) [NCBI Gene 20209] {aka Saa-2, Saa1}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, Saa1 (serum amyloid A 1) [NCBI Gene 20208] {aka Saa-1, Saa2}, Cxcl1 (C-X-C motif chemokine ligand 1) [NCBI Gene 14825] {aka Fsp, Gro1, KC, Mgsa, N51, Scyb1}, GCGR (glucagon receptor) [NCBI Gene 2642] {aka GGR, GL-R, MVAH}, FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Glp1r (glucagon-like peptide 1 receptor) [NCBI Gene 14652] {aka GLP-1R, GLP1Rc}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, Gcgr (glucagon receptor) [NCBI Gene 14527] {aka GR}, Gip (gastric inhibitory polypeptide) [NCBI Gene 14607], Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc} - **Diseases:** thyroid C-cell tumors (MESH:D013968), Chronic hepatic inflammation (MESH:D006521), MASLD (MESH:D008107), hepatic inflammation (MESH:D007249), Fibrosis (MESH:D005355), metabolic syndrome (MESH:D024821), hepatic fibrosis (MESH:D008103), pancreatitis (MESH:D010195), NAFLD (MESH:D065626), diabetes (MESH:D003920), Hepatic steatosis (MESH:D005234), obese (MESH:D009765), metabolic derangements (MESH:D008659), gastrointestinal side effects (MESH:D064420), weight loss (MESH:D015431), insulin resistance (MESH:D007333), hypoglycemia (MESH:D007003), gastrointestinal intolerance (MESH:D005767), hepatic injury (MESH:D056486), systemic (MESH:D015619), liver condition (MESH:D017093), T2DM (MESH:D003924), hepatic fat (MESH:D005218), nausea and vomiting (MESH:D020250), adiposity (MESH:D018205), DKD (MESH:D003928), HCC (MESH:D006528), lipid (MESH:D011017) - **Chemicals:** triglyceride (MESH:D014280), vitamin E (MESH:D014810), exendin-4 (MESH:D000077270), cholesterol (MESH:D002784), cAMP (MESH:D000242), GLP-1RA (-), fatty acid (MESH:D005227), palmitic acid (MESH:D019308), Lipid (MESH:D008055), Resmetirom (MESH:C588408), Pioglitazone (MESH:D000077205), fructose (MESH:D005632), RAs (MESH:D011883), glucose (MESH:D005947) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606] - **Cell lines:** HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), /2 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12935680/full.md ## Figures 1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12935680/full.md ## References 58 references — full list in the complete paper: https://tomesphere.com/paper/PMC12935680/full.md --- Source: https://tomesphere.com/paper/PMC12935680