In particular, despite the paradoxically elevated expression of FGF21 in people with NAFLD/MASLD, which correlates with liver histopathology [78], its beneficial effects on energy homeostasis through hypothalamic actions, as well as direct benefits on adipose tissue (e.g., improvement of insulin sensitivity) and the liver (reduction in lipid overload), have led to considerable efforts in the last decade to develop FGF21 derivatives or specific FGF21 agonists for the treatment of various metabolic disorders, including T2D, obesity, and NAFLD [79]. This evidence concerns the gene FGF21 and metabolic dysfunction-associated steatotic liver disease.