PLX3397 data

Proliferation of microglia in the central nervous system (CNS) has recently been linked with consumption of high energy diets (HEDs) and diet-induced obesity (DIO). Here we used diet adulteration with the CSF-1R antagonist PLX 3397 (Pexidartinib; PLX) to study the effects of suppression of microglia activation on body weight, body composition and sucrose preference in lean and DIO male and female rats. Microglia activation was quantified in the hypothalamus and the nucleus tractus solitarius (NTS). PLX tended to increase body weight in males but decrease body weight in females when added to the initial exposure of a HED. PLX+HED decreased percent body fat in male DIO rats but did not affect body weight in either sex. PLX effects were more widespread across hypothalamic nuclei in male vs. female rats; however, PLX induced similar suppression of microglia activation in the NTS of both sexes. PLX rescued the HED-induced suppression of low-concentration sucrose preference in male rats in the Chow/HED+PLX group. Significant individual differences were apparent in both susceptibility to DIO and efficacy of PLX. Our data demonstrate a sexual dimorphism in the inflammatory response to a HED where females are protected, and males are potentially more vulnerable to adverse metabolic consequences.

Procedures used in this study were approved by the IACUC at Binghamton University (Protocol title: Temporal coding in the gustatory system of the rat; Protocol #: 735-15, 2015-2018). All procedures were in accord with the National Institutes of Health Animal Welfare Guide.