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.
Keyphrases
- high fat diet
- dna methylation
- genome wide
- single cell
- rna seq
- insulin resistance
- high fat diet induced
- gene expression
- high throughput
- adipose tissue
- metabolic syndrome
- dna damage
- copy number
- type diabetes
- skeletal muscle
- transcription factor
- weight loss
- electronic health record
- induced apoptosis
- circulating tumor cells
- white matter
- resting state
- signaling pathway
- cell cycle arrest
- cell death
- multiple sclerosis
- single molecule
- physical activity
- blood brain barrier
- nucleic acid
- machine learning
- body mass index
- cell proliferation