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DMF upregulates DNA hydroxymethylation We first determined whether DMF treatment mediates global or CBS locus-specific DNA methylation/hydroxymethylation (5mC/5hmC) modifications

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Abbreviations AC: Adenylate cyclase ATP: Denosine triphosphate BAT: Brown adipose tissue BCAAs: Branched-chain amino acids BCKA: Branched-chain keto acids BMI: Body mass index cAMP: Cyclic adenosine monophosphate CNS: Central nervous system CREB: CAMP response element-binding DIO: Diet-induced obesity DPP- 4: Dipeptidyl peptidase- 4 EGFR: Epidermal growth factor receptor EPACs: Exchange proteins directly activated by Camp Foxo1: Nuclear transcription factor GIP: Glucose-dependent insulinotropic polypeptide GIPRAb: GIP receptor antagonist antibody GPCRs: G-protein-coupled receptors GTP: Guanine triphosphate HbA1c: Glycated haemoglobin HSL: Hormone-sensitive lipase ICV: Intracerebroventricular IR: Insulin resistance LAGIPRA: Long-acting GIP receptor agonist MAPK: Mitogen activated protein kinase MASLD: Metabolically associated steatotic liver disease PI3 K-PKB/Akt: Phosphoinositide- 3-kinaseprotein kinase B/Akt PKA: Protein kinase A SUR1: Sulfonylurea receptor 1 T2DM: Type 2 diabetes mellitus TORCs: Transducers of regulated CREB protein activity ZDF: Zucker diabetic fatty References Murray CJL, Aravkin AY, Zheng P, et al

Bottom line: No receptor desensitization issue