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.
Footnotes
The authors declare no competing financial interests.
This work was supported by the Spanish Ministry, Industry of Economy and Competitiveness (MEIC) to the EMBL partnership; “Centro de Excelencia Severo Ochoa CERCA Programme / Generalitat de Catalunya”; the Centro de Investigación Biomédica en Red Enfermedades Raras (CIBER) of Rare Diseases; Departamento de Innovación, Universidadesy Empresa (DIUE) de la Generalitat de Catalunya [Grups consolidats SGR 2014/1125]; Spanish Ministry, Industry of Economy and Competitiveness (MEIC) [SAF2013-49129-C2-1-R and SAF2016-79956-R, Jerôme Lejeune Foundation]; Centro para el Desarrollo Tecnológico Industrial CDTI [“Smartfoods”]; This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement N°608959 (IMPULSE) and the Polish National Center for Research and Development grant [ERA-NET-NEURON/10/2013 to B.W. and I.E.G.]. New affiliation for IG: Institute of Computer Science Polish Academy of Sciences.
I.D.T. and I.E.G. are joint first authors.
I. E. Grabowicz’s present address: Institute of Computer Science Polish Academy of Sciences. ul. Jana Kazimierza 5, Warsaw, Poland.
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