The Hypothalamic Epigenetic Landscape in Dietary Obesity

The hypothalamus in the brain plays a pivotal role in controlling energy balance in vertebrates. Nutritional excess through high-fat diet (HFD) feeding can dysregulate hypothalamic signaling at multiple levels. Yet, it remains largely unknown in what magnitude HFD feeding may impact epigenetics in this brain region. Here, it is shown that HFD feeding can significantly alter hypothalamic epigenetic events, including posttranslational histone modifications, DNA methylation, and chromatin accessibility. The authors comprehensively analyze the chromatin immunoprecipitation-sequencing (ChIP-seq), methylated DNA immunoprecipitation-sequencing (MeDIP-seq), single nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq), and RNA-seq data of the hypothalamus of C57 BL/6 mice fed with a chow or HFD for 1 to 6 months. The chromatins are categorized into 6 states using the obtained ChIP-seq data for H3K4me3, H3K27ac, H3K9me3, H3K27me3, and H3K36me3. A 1-month HFD feeding dysregulates histone modifications and DNA methylation more pronouncedly than that of 3- or 6-month. Besides, HFD feeding differentially impacts chromatin accessibility in hypothalamic cells. Thus, the epigenetic landscape is dysregulated in the hypothalamus of dietary obesity mice. The impact of feeding mice a high-fat diet on the epigenetic landscape of the hypothalamus is evaluated. A 1-month HFD feeding exhibits more pronounced dysregulation of histone modifications and DNA methylation than that of 3- or 6-month. HFD feeding differentially impacts chromatin accessibility in hypothalamic cells. Thus, in the hypothalamus of mice with dietary obesity, the epigenetic landscape is dysregulated.image