At first sight, this result seems puzzling since both a decrease in FGF21 levels as well as an increase in HMW adiponectin could indicate metabolic improvements in the context of obesity (Kim et al., 2007; Lee and Shao, 2014; Stern et al., 2016; Gómez-Ambrosi et al., 2017). Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.