In this line, our data provide evidence that (i) obesity and CC increased IL36G and IL36R mRNA expression in VAT; (ii) hypoxia and the inflammation-related factors LPS, TNF-α and leptin increased gene expression levels of IL36G in HT-29 cells; (iii) IL-36γ influenced the expression of key inflammation- and ECM remodelling-related genes in CC cells and (iv) ACM from patients with obesity upregulated the mRNA levels of IL36G in HT-29 cells. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.