The significant increase in serum levels as well as tissue content of IL-6 and sIL-6Rα observed from 8 to 16 weeks of HFD feeding in both IL-6RαT-KO and their control IL-6Rαf/f confers an upregulated IL-6 trans-signalling during prolonged progression of diet-induced obesity (Fig. 7). Here, IL6 is linked to obesity due to melanocortin 4 receptor deficiency.