FGF21 and obesity due to melanocortin 4 receptor deficiency: Due to the increased circulating levels of FGF-21, a higher concentration threshold of the hormone may be required in obesity for the activation of the related pathways, and this may explain the potential role of exogenous supplementation of the hormone as treatment for metabolic disease, as demonstrated by the results of phase II clinical studies showing benefits in ameliorating MASLD and adiposity [30].