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Abbreviations 1 H-MRS: proton magnetic resonance spectroscopy ACC: acetyl-CoA carboxylase ALT: alanine aminotransferase AMPK: adenosine monophosphate-activated protein kinase apoB100: apolipoprotein B100 AST: aspartate aminotransferase AUROC: area under receiver operator characteristic BARD score: BMI, AST/ALT ratio, Diabetes BMI: body mass index BSH: bile salt hydrolase CAP: controlled attenuation parameter ChREBP: carbohydrate regulatory element binding protein DNL: de novo lipogenesis EASL: European Association for the Study of Liver EBMT: endoscopic bariatric and metabolic treatment ELF: enhanced liver fibrosis score FAS: fatty acid synthase FFA: free fatty acid FGF: fibroblast growth factor FXR: farnesoid x receptor GH: growth hormone GI: gastrointestinal GIP: glucose-dependent insulinotropic polypeptide GLP1: glucagon like peptide 1 GLP1-Ras: glucagon-like peptide-1 receptor agonist GLUT4: glucose transporter 4 HDL: high-density lipoprotein HTGC: hepatic triglyceride content IGF1: insulin-like growth factor-1 IR: insulin resistance LSM: liver stiffness measurement MAFLD: metabolic dysfunction-associated fatty liver disease MRE: magnetic resonance elastography MRI-PDFF: magnetic resonance imaging-proton density fat fraction MTTP: microsomal triglyceride transfer protein NAFLD: nonalcoholic fatty liver disease NASH: nonalcoholic steatohepatitis NF-B: nuclear factor kappa B PLNPLA3: patatin-like phospholipase domain-containing protein 3 PPAR: peroxisome proliferator-activated receptor RBP4: retinol-binding protein 4 ROS: reactive oxygen species SAF: steatosis, activity, and fibrosis SCFA: short-chain fatty acid SGLT2i: sodium-glucose cotransporter 2 inhibitor SREBP1c: sterol regulatory element binding protein 1c T2DM: type 2 diabetes mellitus TIMP1: tissue inhibitor of metalloprotease-1 TM6SF2: transmembrane 6 superfamily member 2 USG: B-mode ultrasonography VCTE: vibration-controlled transient elastography VLDL: very low-density lipoprotein Declarations Acknowledgement None

Several conditions leading to ROS generation in cells have been proposed, among which are hyperglycemia, hyperlipidemia, hypoxia, and endoplasmic reticulum (ER)

Pharmacological or gene inhibition of glutathione transporters, including multidrug resistant protein 1, can block cell GSH release, reduce intracellular ROS levels and production of oxidized phosphatidylcholine, thereby inhibiting cell ferroptosis

Most dual-compound research focuses instead on combining tirzepatide with other peptide classes (e.g., glucagon receptor agonists or amylin analogs) or stacking low-dose tirzepatide with oral semaglutide to balance efficacy and tolerability

3ln), whereas cystine levels were not (Fig

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