Plasma concentration of FGF21, an adipokine whose concentration is increased in patients with obesity, was increased in 10-month-old animals; the increased concentration of plasma FGF21 in mice of both genotypes fed with a HFD at the age of 10 months could compensate for insulin resistance and finally increase tolerance to glucose through increased glucose uptake by insulin-sensitive tissues, which could be partly demonstrated by increased protein levels of GLUT4 in muscle and eWAT [42]. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.