Obesity can induce a phenotypic shift of ATMs from M2 to M1, with pro-inflammatory cytokines such as TNF-α, interleukin (IL)-1, and IL-6, which are particularly secreted by M1 ATMs, exacerbating insulin resistance and contributing to local or systemic metabolic dysfunction (129, 130, 131, 132). This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.