TNF and obesity due to melanocortin 4 receptor deficiency: This is underpinned by the finding that ZAG is downregulated by pro-inflammatory mediators such as TNF-α: an inverse correlation between ZAG and TNF-α, VCAM-1, MCP-1 and CRP has been observed in patients suffering from systemic inflammation associated with chronic kidney disease, obesity and metabolic syndrome [40–42].