In a 2003 study, Weisberg et al. demonstrated that the number of adipose tissue macrophages increases in obesity, participating in activated inflammatory pathways; the researchers proved that adipose tissue macrophages (ATM) in obese individuals were responsible for significant proportions of the expression of inducible nitric oxide synthase (iNOS) and IL-6; most importantly, ATM were responsible for nearly all of the expression of TNF-α [46]. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.