Overweight Mice Show Coordinated Homeostatic and Hedonic Transcriptional Response across Brain

Abstract

Obesogenic diets lead to overeating and obesity by inducing the expression of genes involved in hedonic and homeostatic responses in specific brain regions. However, how the effects on gene expression are coordinated in the brain so far remains largely unknown. In our study, we provided mice with access to energy-dense diet, which induced overeating and overweight, and we explored the transcriptome changes across the main regions involved in feeding and energy balance: hypothalamus, frontal cortex, and striatum. Interestingly, we detected two regulatory processes: a switch-like regulation with differentially expressed (DE) genes changing over 1.5-fold and “fine-tuned” subtler changes of genes whose levels correlated with body weight and behavioral changes. We found that genes in both categories were positioned within specific topologically associated domains (TADs), which were often differently regulated across different brain regions. These TADs were enriched in genes relevant for the physiological and behavioral observed changes. Our results suggest that chromatin structure coordinates diet-dependent transcriptional regulation.

Identifying of immune‐associated genes for assessing the obesity‐associated risk to the offspring in maternal obesity: A bioinformatics and machine learning

“…Background calibration, normalization, and log2 transformation were performed on the GSE135830 and GSE127056 datasets using Limma in R. When multiple probes were used to identify the same gene, the average value was calculated to determine the expression level. According to previous studies on the transcriptomics of the diet‐induced obesity (DIO) animal models, the gene expression changes related to obesity are usually at a modest and even subtle level 14,15 . As previously described, a fold change (FC) above 1.5 (i.e., |log 2 FC| > 0.585) and p value < 0.05 were set as the criteria for identifying DEGs using the Limma package 14,15 …”

“…According to previous studies on the transcriptomics of the diet‐induced obesity (DIO) animal models, the gene expression changes related to obesity are usually at a modest and even subtle level. 14 , 15 As previously described, a fold change (FC) above 1.5 (i.e., |log 2 FC| > 0.585) and p value < 0.05 were set as the criteria for identifying DEGs using the Limma package. 14 , 15 …”

“… 14 , 15 As previously described, a fold change (FC) above 1.5 (i.e., |log 2 FC| > 0.585) and p value < 0.05 were set as the criteria for identifying DEGs using the Limma package. 14 , 15 …”