We found, for the first time, that: i) the increased circulating levels of IL-36γ in patients with obesity decreased after weight and fat loss achieved by bariatric surgery, and ii) gene expression levels of IL36G were upregulated in the VAT from patients with obesity, whereas its receptor is only augmented in the VAT from patients with obesity-associated T2D. Here, IL36G is linked to obesity due to melanocortin 4 receptor deficiency.