INS and obesity due to melanocortin 4 receptor deficiency: To demonstrate the utility of our MPS representing the WAT-liver axis for drug discovery, we selected two well-recognized insulin sensitizers (metformin at 10 mM and rosiglitazone at 1 μM) and one anti-inflammatory drug (dexamethasone at 0.5 μM) to assess their efficacy in treating obesity-induced MASLD/T2DM in the M1-iADIPO-iHEP-MPS (Fig. 3a).