However, upon a HFD, although obesity was exacerbated and glucose tolerance decreased in TIMP2−/− mice from both sexes (male were more intolerant to glucose than female mice), only male TIMP2−/− mice were insulin resistant with increased pancreatic β-cell mass and hyperplasia compared to controls [170], suggesting sex-diet interactions when TIMP2 is inactivated. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.