Effect of brain specific deletion of PPARγ on puberty onset, hypothalamic gene expression and diet induced obesity (DIO) in C57BL/6 mice

Abstract

Proliferator‐activated receptor gamma (PPARγ) ligands have been used for the treatment of insulin resistance in type 2 diabetes and polycystic ovary syndrome. We created a neuronal‐specific deletion of PPARγ (BKO) by crossing a floxed PPARγ mouse to a Synapsin‐cre mouse and assessed the effect of the gene deletion on reproduction. Male and female BKO mice exhibited reduced litter sizes; females also showed elevated pituitary LHβ mRNA and serum LH levels and hemorrhagic corpora lutea with reduction of primary and secondary follicles in the ovary. Male BKO mice also showed increased tubular degeneration in the testis. Female BKO mice did not exhibit alterations in the onset of puberty, nor did we observe alterations in hypothalamic GnRH in proestrus or estrus, or Kiss1 and TRH mRNA in estrus. We have previously published that BKO male mice are resistant to diet‐induced obesity (DIO) and leptin‐sensitive. Female BKO and control littermates do not show differences in their fasting basal glucose levels or glucose tolerance tests when fed normal chow, similar to the male BKO mice. The effects of DIO on reproduction are being assessed by putting BKO and control mice on a 60% high‐fat diet or a 10% fat control diet, and we will present data on glucose and leptin sensitivity, as well as basal and GnRH‐stimulated gonadotropin levels and estrous cyclicity to further understand the role of brain PPARγ in modulating reproduction. Supported by NIH grant U54HD12303.