Abstract
| Originalsprog | Engelsk |
|---|
| Udgivelsessted | Copenhagen |
|---|---|
| Forlag | Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen |
| Antal sider | 117 |
| Status | Udgivet - 2016 |
Note vedr. afhandling
The human studies were conducted at the University of Copenhagen, Department of Nutrition, Exercise, and Sports. Furthermore, as a part of the PhD work, analysis of plasma alkylresorcinols and setting up a method for analyzing one-carbon metabolites were carried out at Chalmers University of Technology, Department of Biology and Biological Engineering, Division of Food Science and Nutrition. The method for analyzing one-carbon metabolites was not finished at the time of the PhD thesis submission and is therefore not included here.Citationsformater
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Copenhagen: Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2016. 117 s.
Publikation: Bog/antologi/afhandling/rapport › Ph.d.-afhandling
}
TY - BOOK
T1 - The Role of Diet in One-Carbon Metabolism and Epigenetics
T2 - A Metabolic Syndrome Perspective
AU - Lind, Mads Vendelbo
PY - 2016
Y1 - 2016
N2 - Background: Dysregulation of one-carbon metabolism (OCM) is related to metabolic syndrome (MetS) through various mechanisms including epigenetics. Diet plays a central role in ensuring normal OCM regulation by supplying multiple nutrients. Foods such as whole grains and fish have been proposed toregulate OCM and thereby potentially affecting MetS via OCM. Whole grain is rich in several OCM nutrients and higher whole grain intake has been associated with lower plasma homocysteine (Hcy) concentrations. Furthermore, fish are rich in vitamin B12 and choline as well as the fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which might also play a role in OCM regulation and epigenetics.Aim: This PhD thesis investigates the role of diet in OCM regulation and the potential association between OCM and MetS. We further investigated whether a dietary intervention with high whole grain intake can affect OCM metabolites in plasma. Finally, we explored whether a fish oil supplement can induce epigenetic changes and whether these are related to MetS features.Methods: In two cross-sectional studies using the 3G-cohort, we investigated associations between plasma OCM metabolites, s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) and Hcy, and diet. Associations between OCM metabolites and MetS features were also investigated. In an 8-week human cross-over intervention study we investigated whether a diet rich in whole grain compared to a diet rich in refined grain could affect OCM metabolites. Finally, we investigated whether supplementing 9-month old infants with fish oil compared to sunflower oil could elicit epigenetic changes, through DNA methylation, and whether this was related to changes in MetS features.Results: OCM metabolites were associated with MetS features, with higher concentrations of SAM, SAH and Hcy being associated with a more adverse risk profile. Different OCM metabolites were independently associated with different MetS features. In the cross-sectional analysis of foods and OCM metabolites, higher whole grain was associated with lower Hcy and higher fish intake was associated with lower Hcy and SAH. No associations were found between EPA, DHA and OCM metabolites. In contrast to the findings in the cross-sectional study, the whole grain intervention trial did not lead to changes in plasma OCM metabolites despite betaine and choline intake being higher in the whole grainperiod. Supplementing fish oil to infants lead to changes in DNA methylation in multiple genes, and some of these methylation changes were associated with changes in MetS features, such as blood pressure and insulin resistance.Conclusion: OCM is associated with MetS features, however, it is still not known whether this is a cause or a consequence of MetS. Specific foods such as whole grain and fish are associated with OCM metabolites, suggesting that OCM could be manipulated by dietary interventions. However, a whole grain intervention did not change OCM metabolites suggesting that alternative interventions should beconsidered. We found that supplementing with fish oil lead to epigenetic changes, but we did not find any evidence that this was linked to OCM. More studies are needed to link foods, OCM, epigenetics and MetS in order to find possible preventive and therapeutic possibilities.
AB - Background: Dysregulation of one-carbon metabolism (OCM) is related to metabolic syndrome (MetS) through various mechanisms including epigenetics. Diet plays a central role in ensuring normal OCM regulation by supplying multiple nutrients. Foods such as whole grains and fish have been proposed toregulate OCM and thereby potentially affecting MetS via OCM. Whole grain is rich in several OCM nutrients and higher whole grain intake has been associated with lower plasma homocysteine (Hcy) concentrations. Furthermore, fish are rich in vitamin B12 and choline as well as the fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which might also play a role in OCM regulation and epigenetics.Aim: This PhD thesis investigates the role of diet in OCM regulation and the potential association between OCM and MetS. We further investigated whether a dietary intervention with high whole grain intake can affect OCM metabolites in plasma. Finally, we explored whether a fish oil supplement can induce epigenetic changes and whether these are related to MetS features.Methods: In two cross-sectional studies using the 3G-cohort, we investigated associations between plasma OCM metabolites, s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) and Hcy, and diet. Associations between OCM metabolites and MetS features were also investigated. In an 8-week human cross-over intervention study we investigated whether a diet rich in whole grain compared to a diet rich in refined grain could affect OCM metabolites. Finally, we investigated whether supplementing 9-month old infants with fish oil compared to sunflower oil could elicit epigenetic changes, through DNA methylation, and whether this was related to changes in MetS features.Results: OCM metabolites were associated with MetS features, with higher concentrations of SAM, SAH and Hcy being associated with a more adverse risk profile. Different OCM metabolites were independently associated with different MetS features. In the cross-sectional analysis of foods and OCM metabolites, higher whole grain was associated with lower Hcy and higher fish intake was associated with lower Hcy and SAH. No associations were found between EPA, DHA and OCM metabolites. In contrast to the findings in the cross-sectional study, the whole grain intervention trial did not lead to changes in plasma OCM metabolites despite betaine and choline intake being higher in the whole grainperiod. Supplementing fish oil to infants lead to changes in DNA methylation in multiple genes, and some of these methylation changes were associated with changes in MetS features, such as blood pressure and insulin resistance.Conclusion: OCM is associated with MetS features, however, it is still not known whether this is a cause or a consequence of MetS. Specific foods such as whole grain and fish are associated with OCM metabolites, suggesting that OCM could be manipulated by dietary interventions. However, a whole grain intervention did not change OCM metabolites suggesting that alternative interventions should beconsidered. We found that supplementing with fish oil lead to epigenetic changes, but we did not find any evidence that this was linked to OCM. More studies are needed to link foods, OCM, epigenetics and MetS in order to find possible preventive and therapeutic possibilities.
UR - https://soeg.kb.dk/permalink/45KBDK_KGL/fbp0ps/alma99122559637805763
M3 - Ph.D. thesis
BT - The Role of Diet in One-Carbon Metabolism and Epigenetics
PB - Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen
CY - Copenhagen
ER -