This integrated and scalable co-culture system supports the mechanistic understanding of metabolic crosstalk underlying obesity, focusing on key markers of metabolism, lipid accumulation and lipid peroxidation such as cluster of differentiation 36 (CD36), PPARγ, glucagon-like peptide 1 (GLP-1) and Resistin (at liver compartment) and AMP-activated protein kinase (AMPK), sterol regulatory element-binding protein-1 (SREBP-1), Perilipin (at adipose level); with particular attention also to gut function and browning mechanism in 3T3-L1 adipocytes. This evidence concerns the gene SREBF1 and obesity due to melanocortin 4 receptor deficiency.