FGF21 and obesity due to melanocortin 4 receptor deficiency: However, when secondary or primary dysfunction occurs in skeletal muscle mitochondria with severe external stimuli (e.g., palmitate or excessive obesity), the signal transduction of FGF21 is severely damaged and even inhibits the expression of p-β-klotho, p-ERK, p-FGFR, and p-FGS2α, ultimately reducing glycogen uptake, and even worse, causing myotube loss [100,101].