Although previous studies reported that physical exercise plays an equivalent role in terms of energy balance (Redman et al., 2007) and regulating insulin resistance (Coker et al., 2009), our data suggest that in mice, caloric restriction might be a more effective intervention in protecting white matter structures than physical exercise as expression of markers of microglia activation and phagocytosis (CD16/CD32, Mac-2, and Dectin-1) was notably absent in the white matter of caloric restriction LFD mice. Here, LGALS3 is linked to Insulin resistance.