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- Eriksson, Anders, et al.
(författare)
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Implication of coronin 7 in body weight regulation in humans, mice and flies
- 2015
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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a growing global concern with strong associations with cardiovascular disease, cancer and type-2 diabetes. Although various genome-wide association studies have identified more than 40 genes associated with obesity, these genes cannot fully explain the heritability of obesity, suggesting there may be other contributing factors, including epigenetic effects. Results: We performed genome wide DNA methylation profiling comparing normal-weight and obese 9-13 year old children to investigate possible epigenetic changes correlated with obesity. Of note, obese children had significantly lower methylation levels at a CpG site located near coronin 7 (CORO7), which encodes a tryptophan-aspartic acid dipeptide (WD)-repeat containing protein most likely involved in Golgi complex morphology and function. Anatomical profiling of coronin 7 (Coro7) mRNA expression in mice revealed that it is highly expressed in appetite and energy balance regulating regions, including the hypothalamus, striatum and locus coeruleus, the main noradrenergic brain site. Interestingly, we found that food deprivation in mice downregulates hypothalamic Coro7 mRNA levels, and injecting ethanol, an appetite stimulant, increased the number of Coro7 expressing cells in the locus coeruleus. Finally, by employing the genetically-tractable Drosophila melanogaster model we were able to demonstrate an evolutionarily conserved metabolic function for the CORO7 homologue pod1. Knocking down the pod1 in the Drosophila adult nervous system increased their resistance to starvation. Furthermore, feeding flies a high-calorie diet significantly increased pod1 expression. Conclusion: We conclude that coronin 7 is involved in the regulation of energy homeostasis and this role stems, to some degree, from the effect on feeding for calories and reward.
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| 2. |
- Rask-Andersen, Mathias, et al.
(författare)
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Association of TMEM18 variants with BMI and waist circumference in children and correlation of mRNA expression in the PFC with body weight in rats
- 2012
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 20:2, s. 192-197
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have shown a strong association of single-nucleotide polymorphisms (SNPs) in the near vicinity of the TMEM18 gene. The effects of the TMEM18-associated variants are more readily observed in children. TMEM18 encodes a 3TM protein, which locates to the nuclear membrane. The functional context of TMEM18 and the effects of its associated variants are as of yet undetermined. To further explore the effects of near-TMEM18 variants, we have genotyped two TMEM18-associated SNPs, rs6548238 and rs4854344, in a cohort of 2352 Greek children (Healthy Growth Study). Included in this study are data on anthropomorphic traits body weight, BMI z-score and waist circumference. Also included are dietary energy and macronutrient intake as measured via 24-h recall interviews. Major alleles of rs6548238 and rs4854344 were significantly associated with an increased risk of obesity (odds ratio=1.489 (1.161-1.910) and 1.494 (1.165-1.917), respectively), and positively correlated to body weight (P=0.017, P=0.010) and waist circumference (P=0.003, P=0.003). An association to energy and macronutrient intake was not observed in this cohort. We also correlated food intake and body weight in a food choice model in rats to Tmem18 expression in central regions involved in feeding behavior. We observed a strong positive correlation between TMEM18 expression and body weight in the prefrontal cortex (PFC) (r=0.5694, P=0.0003) indicating a potential role for TMEM18 in higher functions related to feeding involving the PFC.
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| 3. |
- Rask-Andersen, Mathias, et al.
(författare)
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The MAP2K5-linked SNP rs2241423 is associated with BMI and obesity in two cohorts of Swedish and Greek children
- 2012
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13, s. 36-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecent genome-wide association studies have identified a single nucleotide polymorphism within the last intron of MAP2K5 associated with a higher body mass index (BMI) in adults. MAP2K5 is a component of the MAPK-family intracellular signaling pathways, responding to extracellular growth factors such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In this study, we examined the association of this variant in two cohorts of children from Sweden and Greece.MethodsWe examine the association of rs2241423 to BMI in a cohort of 474 Swedish children admitted for treatment of childhood obesity and 519 children matched for gender, ethnicity and socioeconomic background from the Stockholm area, as well as a cross-sectional cohort of 2308 Greek school children (Healthy Growth Study). Children were genotyped using a predesigned TaqMan polymorphism assay. Logistic regression was used to test for an association of rs2241423 to obesity in the cohort of Swedish children. Linear regression was used to test for an association of rs2241423 to BMI z-score and phenotypic measurements of body adiposity in the cohort of Greek children. Models were adjusted for age and gender. In the cohort of Greek children the model was also adjusted for stage of pubertal development.ResultsThe minor allele of rs2241423, allele A, was associated with a protective effect against obesity in the cohort of Swedish children (p = 0.029, OR = 0.79 (95% CI: 0.64-0.98)), and with a lower BMI z-score in the cohort of Greek children (p = 0.028, beta = -0.092). No association to phenotypic measurements of body fat distribution could be observed in our study.Conclusionsrs2241423 was associated with BMI and obesity in two independent European cohorts suggesting a role for MAP2K5 in early weight regulation.
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| 4. |
- Voisin, Sarah, et al.
(författare)
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Dietary fat quality impacts genome-wide DNA methylation patterns in a cross-sectional study of Greek preadolescents
- 2015
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 23, s. 654-662
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Tidskriftsartikel (refereegranskat)abstract
- The type and the amount of dietary fat have a significant influence on the metabolic pathways involved in the development of obesity, metabolic syndrome, diabetes type 2 and cardiovascular diseases. However, it is unknown to what extent this modulation is achieved through DNA methylation. We assessed the effects of cholesterol intake, the proportion of energy intake derived from fat, the ratio of polyunsaturated fatty acids (PUFA) to saturated fatty acids (SFA), the ratio of monounsaturated fatty acids (MUFA) to SFA, and the ratio of MUFA+PUFA to SFA on genome-wide DNA methylation patterns in normal-weight and obese children. We determined the genome-wide methylation profile in the blood of 69 Greek preadolescents (∼10 years old) as well as their dietary intake for two consecutive weekdays and one weekend day. The methylation levels of one CpG island shore and four sites were significantly correlated with total fat intake. The methylation levels of 2 islands, 11 island shores and 16 sites were significantly correlated with PUFA/SFA; of 9 islands, 26 island shores and 158 sites with MUFA/SFA; and of 10 islands, 40 island shores and 130 sites with (MUFA+PUFA)/SFA. We found significant gene enrichment in 34 pathways for PUFA/SFA, including the leptin pathway, and a significant enrichment in 5 pathways for (MUFA+PUFA)/SFA. Our results suggest that specific changes in DNA methylation may have an important role in the mechanisms involved in the physiological responses to different types of dietary fat.European Journal of Human Genetics advance online publication, 30 July 2014; doi:10.1038/ejhg.2014.139.
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