title: A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels.
abstract: 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.
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Wiemerslage
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Islam
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: C
authors.initials: C
authors.lastname: van der Kamp
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Cao
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Olivo
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Ence-Eriksson
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Castillo
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: A L
authors.initials: AL
authors.lastname: Larsen
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bandstein
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: L S
authors.initials: LS
authors.lastname: Dahlberg
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Perland
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Gustavsson
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Nilsson
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Vogel
authors.affiliation: German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schürmann
authors.affiliation: Radiology Unit, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: E-M
authors.initials: EM
authors.lastname: Larsson
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Rask-Andersen
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Benedict
authors.affiliation: Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala Sweden.
authors.forename: H B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000818:Animals; D001069:Appetite Regulation; D001921:Brain / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005247:Feeding Behavior / Q000502:physiology; D059907:Functional Neuroimaging; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D000068797:Orexins / Q000378:metabolism*; D054440:Receptors, Ghrelin / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012201:Reward
chemical_list: D018797:Cell Cycle Proteins; D054439:Ghrelin; C486423:KLF13 protein, human; D051741:Kruppel-Like Transcription Factors; D000068797:Orexins; D054440:Receptors, Ghrelin; D012097:Repressor Proteins