TNF and obesity due to melanocortin 4 receptor deficiency: Indeed, pharmacological mTORC1 inhibition with the macrolide rapamycin is associated with an exacerbation of obesity-associated adipose tissue inflammation, as evidenced by the enhanced tissue recruitment and polarization of macrophages to a proinflammatory phenotype and expression of proinflammatory cytokines IL-1β and TNF-α [104, 105].