In this context, there is ample evidence that adipose‐initiated signals are capable to convey extra‐adipose tissue effects8, 41 and patients with obesity and type 2 diabetes have a pronounced proinflammatory signature in adipose tissue‐resistant macrophages driven by NLRP3‐dependent IL‐1β production.42 Here, NLRP3 is linked to obesity due to melanocortin 4 receptor deficiency.