FGF21 and obesity due to melanocortin 4 receptor deficiency: Certainly, at this point, our study lacks an instrumental evaluation for determining energy expenditure; additionally, to better understand the true nature of the FGF-21 resistance state, further mechanistic insights should be provided, particularly regarding modifications in the downstream signalling of the FGF-21 pathway in obesity, but in our opinion this intriguing hypothesis still merit to be further tested in the future.