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N Engl J Med 2016

Over-interpretation of secondary outcomes may lead to spurious inferences, underscoring the need for caution when translating these findings into clinical reassurance.This aligns with emerging data linking metabolic improvements such as weight loss, insulin sensitivity, and reduced inflammation to decreased malignancy risk in high-risk populations with type 2 diabetes or obesity (Marso et al., 2016a

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Abbreviations T2DM: Type 2 diabetes mellitus IL-6: Interleukin-6 TNFa: Tumor necrosis factor- LEPR: Leptin-receptor POMC: Proopiomelanocortin MSH: Melanocyte-stimulating hormone MC4R: Melanocortin-4-receptor LEP: Leptin LPS: Lipopolysaccharide Th: T helper cell DSS: Dextran sulfate sodium NK cells: Natural killer cells INF: Interferon- IgE: Immunoglobulin E NO: Nitric oxide Gro: Growth-regulated protein NFB: Nuclear factor kappa-light-chain-enhancer of activated B cells MC1R: Melanocortin-1-receptor SIRS: Systemic inflammatory response syndrome FDA: Food and Drug Administration EMA: European Medicines Agency CCL2: Chemokine CC motif ligand 2 CXCL10: C-X-C motif chemokine 10 CNS: Central nervous system UPR: Unfolded protein response pathway TLR: Toll-like receptors JNK1: Janus kinase 1 MCP1: Monocyte chemoattractant protein-1 CVD: Cardiovascular diseases VCAM1: Vascular cell adhesion molecule 1 M1: Macrophage type 1 HFD: High-fat diet ATM: Adipose tissue macrophage DIO: Diet-induced obesity UCP2: Uncoupling protein 2 ROS: Reactive oxygen species CRP: C-reactive protein SOCS3: Suppressor of cytokine signaling 3 JAK: Janus kinase STAT: Signal transducer and activator of transcription GIP: Glucose-dependent insulinotropic polypeptide GLP-1: Glucagon-like peptide 1 GIPR: GIP receptor GLP-1R: GLP-1 receptor GLP-1RA: GLP-1 receptor agonists NASH: Non-alcoholic steatohepatitis MACE: Major adverse cardiovascular event MS: Multiple sclerosis EAE: Experimental autoimmune encephalitis TGF: Transforming growth factor IRS-1: Insulin receptor substrate 1 RHM: Recruited hepatic macrophage HSC: Hepatic stellate cells NAFLD: Non-alcoholic fatty liver disease FFA: Free fatty acid AGE: Advanced glycation end product References Seki H, Tani Y, Arita M (2009) Omega-3 PUFA derived anti-inflammatory lipid mediator resolvin E1