TY - JOUR T1 - Overweighed mice show coordinated homeostatic and hedonic transcriptional response across brain JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0287-18.2018 SP - ENEURO.0287-18.2018 AU - I. De Toma AU - I. E. Grabowicz AU - M. Fructuoso AU - D. Trujillano AU - B. Wilczynski AU - M. Dierssen Y1 - 2018/11/26 UR - http://www.eneuro.org/content/early/2018/11/22/ENEURO.0287-18.2018.abstract N2 - 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 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 associating 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.Significance Statement Mice fed with free-choice access to chocolate mixture become overweight and compulsive, recapitulating what happens during obesity. For the first time, we correlated these physical and behavioural changes with the transcriptome in the frontal cortex and the striatum, involved in the hedonic “liking” associated to eating, and the hypothalamus, involved in the homeostasic regulation of food intake. We detected two groups of genes: some transcript were strongly deregulated in term of fold changes; while others were only subtly deregulated but were especially correlating with measurements associated with body-weight and compulsivity. These genes were not randomly distributed, but were positioned in chromatin domains, many of which rich in genes differentially co-regulated across brain areas. ER -