As secondary objectives, we aimed to (i) determine the gene expression levels of NTN1 and NEO1 in actively metabolic tissues [VAT, liver, and peripheral blood mononuclear cells (PBMC)] from lean (LN) volunteers and patients with obesity (OB); (ii) analyze the regulation of NTN1 and NEO1 by hypoxia and different inflammation-related mediators in human visceral adipocytes and in THP-1-derived macrophages and finally, (iii) to disentangle the effects of NTN-1 in inflammation and the remodeling of the extracellular matrix (ECM) in human adipocytes. Here, NTN1 is linked to obesity due to melanocortin 4 receptor deficiency.