Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1
Mid-to-late gestation is a unique period in which women experience dynamic changes in lipid metabolism. Although the recent intensive epigenome-wide association studies (EWAS) using peripheral leukocytes have revealed that lipid-related traits alter DNA methylation, the influence of pregnancy-induce...
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| Veröffentlicht in: | International journal of molecular sciences 2019-03, Vol.20 (5), p.1066 |
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| creator | Pavethynath, Shilpa Imai, Chihiro Jin, Xin Hichiwa, Naomi Takimoto, Hidemi Okamitsu, Motoko Tarui, Iori Aoyama, Tomoko Yago, Satoshi Fudono, Ayako Muramatsu, Masaaki Miyasaka, Naoyuki Sato, Noriko |
| description | Mid-to-late gestation is a unique period in which women experience dynamic changes in lipid metabolism. Although the recent intensive epigenome-wide association studies (EWAS) using peripheral leukocytes have revealed that lipid-related traits alter DNA methylation, the influence of pregnancy-induced metabolic changes on the methylation levels of these differentially methylated sites is not well known. In this study, we performed a prospective cohort study of pregnant women (
= 52) using the MassARRAY EpiTYPER assay and analyzed the methylation levels of variably methylated sites, including
intron 1 and
intron 1 CpGs, which were previously verified to be robustly associated with adiposity traits. Although methylation of
was associated with body mass index (BMI) and low-density lipoprotein cholesterol at mid-gestation, this association was attenuated at late gestation, which was consistent with the metabolic switch from an anabolic to a catabolic state. However, the BMI association with
intron 1 methylation appeared to strengthen at late gestation; this association was mediated by pre-pregnancy BMI-dependent change in the leukocyte proportion during mid-to-late gestation. Thus, the methylation of adiposity-related differentially methylated regions was sensitive to metabolic and immunological changes during mid-to-late gestation. |
| doi_str_mv | 10.3390/ijms20051066 |
| format | Article |
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= 52) using the MassARRAY EpiTYPER assay and analyzed the methylation levels of variably methylated sites, including
intron 1 and
intron 1 CpGs, which were previously verified to be robustly associated with adiposity traits. Although methylation of
was associated with body mass index (BMI) and low-density lipoprotein cholesterol at mid-gestation, this association was attenuated at late gestation, which was consistent with the metabolic switch from an anabolic to a catabolic state. However, the BMI association with
intron 1 methylation appeared to strengthen at late gestation; this association was mediated by pre-pregnancy BMI-dependent change in the leukocyte proportion during mid-to-late gestation. Thus, the methylation of adiposity-related differentially methylated regions was sensitive to metabolic and immunological changes during mid-to-late gestation.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20051066</identifier><identifier>PMID: 30823689</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adiposity - genetics ; Adult ; Blood cells ; Body Mass Index ; Body weight gain ; Carnitine O-Palmitoyltransferase - genetics ; Carnitine O-Palmitoyltransferase - metabolism ; Cholesterol, LDL - blood ; CpG islands ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Epigenetics ; Fatty acids ; Female ; Fetuses ; Gene expression ; Gestation ; Gestational Weight Gain - genetics ; Humans ; Immunology ; Leukocytes (neutrophilic) ; Lipid metabolism ; Lipids ; Lipoproteins ; Lymphocytes ; Metabolism ; Monocytes ; Neutrophils ; Obesity ; Physiology ; Pregnancy ; Pregnancy Trimester, Third ; Sterol Regulatory Element Binding Protein 1 - genetics ; Sterol Regulatory Element Binding Protein 1 - metabolism ; Studies ; Triglycerides ; Womens health</subject><ispartof>International journal of molecular sciences, 2019-03, Vol.20 (5), p.1066</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-36a15d5a034e0c29f6a8701bf271e4d3b49a95ba5f9da8ba68e8d2c62d8b1cc13</citedby><cites>FETCH-LOGICAL-c562t-36a15d5a034e0c29f6a8701bf271e4d3b49a95ba5f9da8ba68e8d2c62d8b1cc13</cites><orcidid>0000-0002-0384-5362 ; 0000-0002-8980-5520 ; 0000-0002-3006-7543 ; 0000-0002-2751-8710</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429071/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429071/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30823689$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pavethynath, Shilpa</creatorcontrib><creatorcontrib>Imai, Chihiro</creatorcontrib><creatorcontrib>Jin, Xin</creatorcontrib><creatorcontrib>Hichiwa, Naomi</creatorcontrib><creatorcontrib>Takimoto, Hidemi</creatorcontrib><creatorcontrib>Okamitsu, Motoko</creatorcontrib><creatorcontrib>Tarui, Iori</creatorcontrib><creatorcontrib>Aoyama, Tomoko</creatorcontrib><creatorcontrib>Yago, Satoshi</creatorcontrib><creatorcontrib>Fudono, Ayako</creatorcontrib><creatorcontrib>Muramatsu, Masaaki</creatorcontrib><creatorcontrib>Miyasaka, Naoyuki</creatorcontrib><creatorcontrib>Sato, Noriko</creatorcontrib><title>Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Mid-to-late gestation is a unique period in which women experience dynamic changes in lipid metabolism. Although the recent intensive epigenome-wide association studies (EWAS) using peripheral leukocytes have revealed that lipid-related traits alter DNA methylation, the influence of pregnancy-induced metabolic changes on the methylation levels of these differentially methylated sites is not well known. In this study, we performed a prospective cohort study of pregnant women (
= 52) using the MassARRAY EpiTYPER assay and analyzed the methylation levels of variably methylated sites, including
intron 1 and
intron 1 CpGs, which were previously verified to be robustly associated with adiposity traits. Although methylation of
was associated with body mass index (BMI) and low-density lipoprotein cholesterol at mid-gestation, this association was attenuated at late gestation, which was consistent with the metabolic switch from an anabolic to a catabolic state. However, the BMI association with
intron 1 methylation appeared to strengthen at late gestation; this association was mediated by pre-pregnancy BMI-dependent change in the leukocyte proportion during mid-to-late gestation. Thus, the methylation of adiposity-related differentially methylated regions was sensitive to metabolic and immunological changes during mid-to-late gestation.</description><subject>Adiposity - genetics</subject><subject>Adult</subject><subject>Blood cells</subject><subject>Body Mass Index</subject><subject>Body weight gain</subject><subject>Carnitine O-Palmitoyltransferase - genetics</subject><subject>Carnitine O-Palmitoyltransferase - metabolism</subject><subject>Cholesterol, LDL - blood</subject><subject>CpG islands</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Epigenetics</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Fetuses</subject><subject>Gene expression</subject><subject>Gestation</subject><subject>Gestational Weight Gain - genetics</subject><subject>Humans</subject><subject>Immunology</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Lipoproteins</subject><subject>Lymphocytes</subject><subject>Metabolism</subject><subject>Monocytes</subject><subject>Neutrophils</subject><subject>Obesity</subject><subject>Physiology</subject><subject>Pregnancy</subject><subject>Pregnancy Trimester, Third</subject><subject>Sterol Regulatory Element Binding Protein 1 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pavethynath, Shilpa</au><au>Imai, Chihiro</au><au>Jin, Xin</au><au>Hichiwa, Naomi</au><au>Takimoto, Hidemi</au><au>Okamitsu, Motoko</au><au>Tarui, Iori</au><au>Aoyama, Tomoko</au><au>Yago, Satoshi</au><au>Fudono, Ayako</au><au>Muramatsu, Masaaki</au><au>Miyasaka, Naoyuki</au><au>Sato, Noriko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2019-03-01</date><risdate>2019</risdate><volume>20</volume><issue>5</issue><spage>1066</spage><pages>1066-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Mid-to-late gestation is a unique period in which women experience dynamic changes in lipid metabolism. Although the recent intensive epigenome-wide association studies (EWAS) using peripheral leukocytes have revealed that lipid-related traits alter DNA methylation, the influence of pregnancy-induced metabolic changes on the methylation levels of these differentially methylated sites is not well known. In this study, we performed a prospective cohort study of pregnant women (
= 52) using the MassARRAY EpiTYPER assay and analyzed the methylation levels of variably methylated sites, including
intron 1 and
intron 1 CpGs, which were previously verified to be robustly associated with adiposity traits. Although methylation of
was associated with body mass index (BMI) and low-density lipoprotein cholesterol at mid-gestation, this association was attenuated at late gestation, which was consistent with the metabolic switch from an anabolic to a catabolic state. However, the BMI association with
intron 1 methylation appeared to strengthen at late gestation; this association was mediated by pre-pregnancy BMI-dependent change in the leukocyte proportion during mid-to-late gestation. Thus, the methylation of adiposity-related differentially methylated regions was sensitive to metabolic and immunological changes during mid-to-late gestation.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>30823689</pmid><doi>10.3390/ijms20051066</doi><orcidid>https://orcid.org/0000-0002-0384-5362</orcidid><orcidid>https://orcid.org/0000-0002-8980-5520</orcidid><orcidid>https://orcid.org/0000-0002-3006-7543</orcidid><orcidid>https://orcid.org/0000-0002-2751-8710</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2019-03, Vol.20 (5), p.1066 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adiposity - genetics Adult Blood cells Body Mass Index Body weight gain Carnitine O-Palmitoyltransferase - genetics Carnitine O-Palmitoyltransferase - metabolism Cholesterol, LDL - blood CpG islands Deoxyribonucleic acid DNA DNA Methylation Epigenetics Fatty acids Female Fetuses Gene expression Gestation Gestational Weight Gain - genetics Humans Immunology Leukocytes (neutrophilic) Lipid metabolism Lipids Lipoproteins Lymphocytes Metabolism Monocytes Neutrophils Obesity Physiology Pregnancy Pregnancy Trimester, Third Sterol Regulatory Element Binding Protein 1 - genetics Sterol Regulatory Element Binding Protein 1 - metabolism Studies Triglycerides Womens health |
| title | Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1 |
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