Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways
Abstract Background Obesity is a negative chronic metabolic health condition that represents an additional risk for the development of multiple pathologies. Epidemiological studies have shown how maternal obesity or gestational diabetes mellitus during pregnancy constitute serious risk factors in re...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-023-01774-y |
| _version_ | 1827985250813214720 |
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| author | Juan José Alba-Linares Raúl F. Pérez Juan Ramón Tejedor David Bastante-Rodríguez Francisco Ponce Nuria García Carbonell Rafael Gómez Zafra Agustín F. Fernández Mario F. Fraga Empar Lurbe |
| author_facet | Juan José Alba-Linares Raúl F. Pérez Juan Ramón Tejedor David Bastante-Rodríguez Francisco Ponce Nuria García Carbonell Rafael Gómez Zafra Agustín F. Fernández Mario F. Fraga Empar Lurbe |
| author_sort | Juan José Alba-Linares |
| collection | DOAJ |
| description | Abstract Background Obesity is a negative chronic metabolic health condition that represents an additional risk for the development of multiple pathologies. Epidemiological studies have shown how maternal obesity or gestational diabetes mellitus during pregnancy constitute serious risk factors in relation to the appearance of cardiometabolic diseases in the offspring. Furthermore, epigenetic remodelling may help explain the molecular mechanisms that underlie these epidemiological findings. Thus, in this study we explored the DNA methylation landscape of children born to mothers with obesity and gestational diabetes during their first year of life. Methods We used Illumina Infinium MethylationEPIC BeadChip arrays to profile more than 770,000 genome-wide CpG sites in blood samples from a paediatric longitudinal cohort consisting of 26 children born to mothers who suffered from obesity or obesity with gestational diabetes mellitus during pregnancy and 13 healthy controls (measurements taken at 0, 6 and 12 month; total N = 90). We carried out cross-sectional and longitudinal analyses to derive DNA methylation alterations associated with developmental and pathology-related epigenomics. Results We identified abundant DNA methylation changes during child development from birth to 6 months and, to a lesser extent, up to 12 months of age. Using cross-sectional analyses, we discovered DNA methylation biomarkers maintained across the first year of life that could discriminate children born to mothers who suffered from obesity or obesity with gestational diabetes. Importantly, enrichment analyses suggested that these alterations constitute epigenetic signatures that affect genes and pathways involved in the metabolism of fatty acids, postnatal developmental processes and mitochondrial bioenergetics, such as CPT1B, SLC38A4, SLC35F3 and FN3K. Finally, we observed evidence of an interaction between developmental DNA methylation changes and maternal metabolic condition alterations. Conclusions Our observations highlight the first six months of development as being the most crucial for epigenetic remodelling. Furthermore, our results support the existence of systemic intrauterine foetal programming linked to obesity and gestational diabetes that affects the childhood methylome beyond birth, which involves alterations related to metabolic pathways, and which may interact with ordinary postnatal development programmes. |
| first_indexed | 2024-04-09T23:11:55Z |
| format | Article |
| id | doaj.art-5c118f504ee24f82997e64060ffde78f |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-04-09T23:11:55Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-5c118f504ee24f82997e64060ffde78f2023-03-22T10:21:01ZengBMCCardiovascular Diabetology1475-28402023-03-0122111810.1186/s12933-023-01774-yMaternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathwaysJuan José Alba-Linares0Raúl F. Pérez1Juan Ramón Tejedor2David Bastante-Rodríguez3Francisco Ponce4Nuria García Carbonell5Rafael Gómez Zafra6Agustín F. Fernández7Mario F. Fraga8Empar Lurbe9Cancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), University of OviedoCancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), University of OviedoCancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), University of OviedoCancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), University of OviedoHealth Research Institute INCLIVAHealth Research Institute INCLIVAHealth Research Institute INCLIVACancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), University of OviedoCancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), University of OviedoHealth Research Institute INCLIVAAbstract Background Obesity is a negative chronic metabolic health condition that represents an additional risk for the development of multiple pathologies. Epidemiological studies have shown how maternal obesity or gestational diabetes mellitus during pregnancy constitute serious risk factors in relation to the appearance of cardiometabolic diseases in the offspring. Furthermore, epigenetic remodelling may help explain the molecular mechanisms that underlie these epidemiological findings. Thus, in this study we explored the DNA methylation landscape of children born to mothers with obesity and gestational diabetes during their first year of life. Methods We used Illumina Infinium MethylationEPIC BeadChip arrays to profile more than 770,000 genome-wide CpG sites in blood samples from a paediatric longitudinal cohort consisting of 26 children born to mothers who suffered from obesity or obesity with gestational diabetes mellitus during pregnancy and 13 healthy controls (measurements taken at 0, 6 and 12 month; total N = 90). We carried out cross-sectional and longitudinal analyses to derive DNA methylation alterations associated with developmental and pathology-related epigenomics. Results We identified abundant DNA methylation changes during child development from birth to 6 months and, to a lesser extent, up to 12 months of age. Using cross-sectional analyses, we discovered DNA methylation biomarkers maintained across the first year of life that could discriminate children born to mothers who suffered from obesity or obesity with gestational diabetes. Importantly, enrichment analyses suggested that these alterations constitute epigenetic signatures that affect genes and pathways involved in the metabolism of fatty acids, postnatal developmental processes and mitochondrial bioenergetics, such as CPT1B, SLC38A4, SLC35F3 and FN3K. Finally, we observed evidence of an interaction between developmental DNA methylation changes and maternal metabolic condition alterations. Conclusions Our observations highlight the first six months of development as being the most crucial for epigenetic remodelling. Furthermore, our results support the existence of systemic intrauterine foetal programming linked to obesity and gestational diabetes that affects the childhood methylome beyond birth, which involves alterations related to metabolic pathways, and which may interact with ordinary postnatal development programmes.https://doi.org/10.1186/s12933-023-01774-yMetabolismDNA methylationEpigeneticsObesityGestational diabetesNewborn |
| spellingShingle | Juan José Alba-Linares Raúl F. Pérez Juan Ramón Tejedor David Bastante-Rodríguez Francisco Ponce Nuria García Carbonell Rafael Gómez Zafra Agustín F. Fernández Mario F. Fraga Empar Lurbe Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways Cardiovascular Diabetology Metabolism DNA methylation Epigenetics Obesity Gestational diabetes Newborn |
| title | Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways |
| title_full | Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways |
| title_fullStr | Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways |
| title_full_unstemmed | Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways |
| title_short | Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways |
| title_sort | maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways |
| topic | Metabolism DNA methylation Epigenetics Obesity Gestational diabetes Newborn |
| url | https://doi.org/10.1186/s12933-023-01774-y |
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