So far, both LPS and long-chain fatty acids, which increase with obesity, have been thought to activate TLR4 expressed on microglia in the induction of hypothalamic chronic inflammation (Sheikh et al 2020; Mendes et al. 2018; Le Thuc et al. 2017) as the underlying mechanism. Here, TLR4 is linked to obesity due to melanocortin 4 receptor deficiency.