News from CRG
Obesity is not just a matter of metabolism. Your behaviour changes and even knowing the unhealthy effects of high fat/high energy diet you cannot stop consuming it. Now scientists at the Centre for Genomic Regulation (CRG) in Barcelona have found out how our genes respond to the foods we eat. They fed mice an obesogenic diet and found that it triggers coordinated gene expression changes in different areas of the brain. The study shows that small changes in the expression of many genes correlate with physical and behavioural changes in the mice, giving clues about how an obesogenic environment can produce behavioural as well as physical alterations that lead to obesity.
They studied gene expression changes in mice which have access to an energy-dense diet. Mice fed the high-energy diet became overweight and compulsive, mimicking what happens as obesity develops in humans. They discovered that the observed gene expression changes are controlled by two main regulatory processes – one molecular ‘switch-like’ process that leads to changes greater than 1.5-fold in a limited number of genes, and another ‘fine tuning’ process which controls genes using a subtler process. Surprisingly, the subtlest molecular changes were the ones associated with body weight and compulsivity.
The research suggests that the gene expression changes induced by a highly palatable and energy-dense diet across different brain regions are orchestrated by chromosomal domains, which allows a coordinated and region-specific response across different brain regions. The fact those genes cluster together in three-dimensional domains suggests epigenetic therapy could be very important, and needs to affect gene expression in a specific 3D region of the genome. We need treatments for obesity that tackle a whole network of genes belonging to key biological processes, rather than a single gene.
I De Toma, I., Grabowicz, I.E., Fructuoso, M., Trujillano, D., Wilczynski, B., Dierssen, M. Overweighed mice show coordinated homeostatic and hedonic transcriptional response across brain. eNeuro (2018). DOI: 10.1523/ENEURO.0287-18.2018