In males, blocking of IL-6 trans-signaling tended to reverse these 3xTg-AD-elicited changes (FGF-21 p = 0.004 R2 = 0.27); in females, in contrast, it tended to further decrease them regardless of the 3xTg-AD genotype (insulin p = 0.031; leptin p = 0.014). Here, INS is linked to Alzheimer disease.