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Abbreviations AI: Artificial intelligence ALK7: Activin receptor-like kinase 7 ALT: Alanine aminotransferase AMH: Anti-Mullerian hormone AMPK: AMP-Activated Protein Kinase ANS: Autonomic nervous system AP: Area postrema BAT: Brown adipose tissue BMI: Body mass index BMP: Bone morphogenic protein cAMP: Adenosine 35-cyclic monophosphate CCK: Cholecystokinin CNS: Central nervous system Cryo-EM: Cryo-electron microscopy CXCL14: Chemokine C-X-C motif chemokine ligand-14 Dab2: Disabled-2 DMN: Dorsal motor nucleus ECM: Extracellular matrix eIF2: Eukaryotic translation initiation factor 2 ERK1/2: Extracellular signal-regulated kinase 1/2 EWL: Essential weight loss FADS2: Fatty acid desaturase 2 FAK: Focal adhesion kinase FGF21: Fibroblast growth factor 21 FFAs: Free fatty acids FoxO1: Forkhead box O1 FXR: Farnesoid X receptor GDFs: Growth differentiation factors GES: Gastric Electrical Stimulation GFRAL: GDNF family receptor -like GLP-1: Glucagon-like peptide 1 GLP-1 RA: GLP-1 receptor agonist HCC: Hepatocellular carcinoma HFD: High-fat diet HSC: Hepatic stellate cell IL-1: Interleukin-1 IL-17RC: Interleukin-17 receptor C JNK: C-Jun N-terminal kinase KLF10: Kruppel-like factor 10 KO: Knockout LTBP1: Latent TGF- binding protein 1 MAPK: Mitogen-activated protein kinase MASLD: Metabolic-associated steatotic liver disease MASH: Metabolic dysfunction-associated steatohepatitis mTORC1: Mammalian target of rapamycin complex 1 NTS: Nucleus of the solitary tract PENS: Percutaneous neurostimulation pFUS: Peripheral focused ultrasound stimulation PGC1: Peroxisome proliferator-activated receptor- coactivator 1- PI3K: Phosphatidylinositol 3-kinase PPARG: Peroxisome proliferator-activated receptor gamma PTEN: Phosphatase and tensin homolog PYY: Peptide tyrosine tyrosine SARA: Smad anchor for receptor activation SETD7: Suppressor of variegation 3-9-enhancer of zeste-trithorax domain containing lysine methyltransferase 7 SHMT2: Serine hydroxymethyl transferase 2 SIX1: Sine oculis homeobox homologue 1 SMIT: Single-molecule fluorescence imaging and tracking SREBP1C: Sterol regulatory element binding proteins 1c STORM: Stochastic optical reconstruction microscopy TG: Triglycerides TGF-: Transforming growth factor- THR-: Thyroid hormone receptor-beta TNF: Tumor necrosis factor T2DM: Type 2 diabetes mellitus UCP1: Uncoupling protein 1 VNS: Vagus nerve stimulation WAT: White adipose tissue WD: Western diet YAP: Yes-associated protein References Al-Khatib SM, Stevenson WG

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Remaining on lower doses substantially reduces weight loss efficacy

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