ABSTRACT
Obesity is a complex disease that is the result of a number of different factors including genetic, environmental, and endocrine abnormalities. Given that monogenic forms of obesity are rare, it is important to identify other mechanisms that contribute to its etiology. Methyl-Cp-G binding protein 2 (MeCP2) is a neuroepigenetic factor that binds to methylated regions of DNA to influence transcription. Past studies demonstrate that disruption in MeCP2 function produces obesity in mice. Using a diet-induced obesity mouse model, we show that perinatal exposure to high fat diet significantly decreases MeCP2 protein expression in the hypothalamus of female mice, effects not seen when high fat diet is given to mice during adulthood. Moreover, these effects are seen specifically in a subregion of the hypothalamus known as the arcuate nucleus with females having decreased MeCP2 expression in rostral areas and males having decreased MeCP2 expression in intermediate regions of the arcuate nucleus. Interestingly, mice gain more weight when exposed to high fat diet during adulthood relative to mice exposed to high fat diet perinatally, suggesting that perhaps high fat diet exposure during adulthood may be affecting mechanisms independent of MeCP2 function. Collectively, our data demonstrate that there are developmentally sensitive periods in which MeCP2 expression is influenced by high fat diet exposure and this occurs in a sexually dimorphic manner.
