Studies in betaine-supplemented mice have demonstrated that betaine may improve glucose homeostasis via upregulation of fibroblast growth factor 21 (Fgf21) [55], an important metabolic regulator, reduce intramyocellular lipid accumulation and insulin resistance [56], and alter the composition of the gut microbiota to favor species associated with obesity prevention [54]. This evidence concerns the gene FGF21 and obesity due to melanocortin 4 receptor deficiency.