We investigated five methylation markers recently linked to body mass index, for their role in the neuropathology of obesity. In neuroimaging experiments, our analysis involving 23 participants showed that methylation levels for the cg07814318 site, which lies within the KLF13 gene, correlated with brain activity in the claustrum, putamen, cingulate gyrus and frontal gyri, some of which have been previously associated to food signaling, obesity or reward. Methylation levels at cg07814318 also positively correlated with ghrelin levels. Moreover, expression of KLF13 was augmented in the brains of obese and starved mice. Our results suggest the cg07814318 site could be involved in orexigenic processes, and also implicate KLF13 in obesity. Our findings are the first to associate methylation levels in blood with brain activity in obesity-related regions, and further support previous findings between ghrelin, brain activity and genetic differences.
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We thank the developers of the Genome Browser, eFP browser and the Allen Brain Atlas for making their online tools free and open to the public. Special thanks to Mikaela Eriksson and Emilia Lekholm (both from the Department of Neuroscience, Uppsala University) for assistance during the preparation of samples from mice. HBS is named guarantor of the article, claiming responsibility for its contents. The study was supported by the Swedish Research Council, the Swedish Brain Research foundation and the German Ministry of Education and Research (BMBF, DZD, grant 01GI0922). ClinicalTrials.gov identifier: NCT01863212.
The authors declare no conflict of interest.
Supplementary Information accompanies this paper on International Journal of Obesity website
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Wiemerslage, L., Islam, R., van der Kamp, C. et al. A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels. Int J Obes 41, 990–994 (2017). https://doi.org/10.1038/ijo.2017.43