{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:34:32Z","timestamp":1791837272329,"version":"4.3.4"},"reference-count":40,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Context: Low birth weight (LBW) and unhealthy diets are risk factors of metabolic disease including type 2 diabetes (T2D). Genetic, nongenetic, and epigenetic data propose a role of the key metabolic regulator peroxisome proliferator-activated receptor \u03b3, coactivator 1\u03b1 (PPARGC1A) in the development of T2D.<\/jats:p>\n               <jats:p>Objective: Our objective was to investigate gene expression and DNA methylation of PPARGC1A and coregulated oxidative phosphorylation (OXPHOS) genes in LBW and normal birth weight (NBW) subjects during control and high-fat diets.<\/jats:p>\n               <jats:p>Design, Subjects, and Main Outcome Measures: Twenty young healthy men with LBW and 26 matched NBW controls were studied after 5 d high-fat overfeeding (+50% calories) and after a control diet in a randomized manner. Hyperinsulinemic-euglycemic clamps were performed and skeletal muscle biopsies excised. DNA methylation and gene expression were measured using bisulfite sequencing and quantitative real-time PCR, respectively.<\/jats:p>\n               <jats:p>Results: When challenged with high-fat overfeeding, LBW subjects developed peripheral insulin resistance and reduced PPARGC1A and OXPHOS (P &amp;lt; 0.05) gene expression. PPARGC1A methylation was significantly higher in LBW subjects (P = 0.0002) during the control diet. However, PPARGC1A methylation increased in only NBW subjects after overfeeding in a reversible manner. DNA methylation of PPARGC1A did not correlate with mRNA expression.<\/jats:p>\n               <jats:p>Conclusions: LBW subjects developed peripheral insulin resistance and decreased gene expression of PPARGC1A and OXPHOS genes when challenged with fat overfeeding. The extent to which our finding of a constitutively increased DNA methylation in the PPARGC1A promoter in LBW subjects may contribute needs to be determined. We provide the first experimental support in humans that DNA methylation induced by overfeeding is reversible.<\/jats:p>","DOI":"10.1210\/jc.2009-2413","type":"journal-article","created":{"date-parts":[[2010,4,22]],"date-time":"2010-04-22T01:48:30Z","timestamp":1271900910000},"page":"3048-3056","source":"Crossref","is-referenced-by-count":167,"title":["Deoxyribonucleic Acid Methylation and Gene Expression of PPARGC1A in Human Muscle Is Influenced by High-Fat Overfeeding in a Birth-Weight-Dependent Manner"],"prefix":"10.1210","volume":"95","author":[{"given":"Charlotte","family":"Br\u00f8ns","sequence":"first","affiliation":[{"name":"Steno Diabetes Center (C.B., S.J., E.N., C.B.J., H.S., P.P., A.V.), Type 2 Diabetes Pathophysiology, 2820 Gentofte, Denmark"},{"name":"Department of Human Nutrition (C.B., A.A.), Faculty of Life Sciences, University of Copenhagen, 1958 Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center (C.B., S.J., E.N., C.B.J., H.S., P.P., A.V.), Type 2 Diabetes Pathophysiology, 2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center (C.B., S.J., E.N., C.B.J., H.S., P.P., A.V.), Type 2 Diabetes Pathophysiology, 2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Ro\u0308nn","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences (T.R., L.G., C.L., A.V.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308 University Hospital, S-205 02 Malmo\u0308, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine B.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center (C.B., S.J., E.N., C.B.J., H.S., P.P., A.V.), Type 2 Diabetes Pathophysiology, 2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Storgaard","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center (C.B., S.J., E.N., C.B.J., H.S., P.P., A.V.), Type 2 Diabetes Pathophysiology, 2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernille","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center (C.B., S.J., E.N., C.B.J., H.S., P.P., A.V.), Type 2 Diabetes Pathophysiology, 2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Groop","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences (T.R., L.G., C.L., A.V.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308 University Hospital, S-205 02 Malmo\u0308, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences (T.R., L.G., C.L., A.V.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308 University Hospital, S-205 02 Malmo\u0308, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Astrup","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition (C.B., A.A.), Faculty of Life Sciences, University of Copenhagen, 1958 Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Vaag","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center (C.B., S.J., E.N., C.B.J., H.S., P.P., A.V.), Type 2 Diabetes Pathophysiology, 2820 Gentofte, Denmark"},{"name":"Department of Clinical Sciences (T.R., L.G., C.L., A.V.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308 University Hospital, S-205 02 Malmo\u0308, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613551583500_R1","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/aje\/kwk071","article-title":"Birth weight and subsequent risk of type 2 diabetes: a meta-analysis","volume":"165","author":"Harder","year":"2007","journal-title":"Am J Epidemiol"},{"key":"2020071613551583500_R2","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1210\/jc.2002-021550","article-title":"Normal insulin-stimulated endothelial function and impaired insulin-stimulated muscle glucose uptake in young adults with low birth weight","volume":"88","author":"Hermann","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613551583500_R3","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1210\/jc.2008-0630","article-title":"Mitochondrial function in skeletal muscle is normal and unrelated to insulin action in young men born with low birth weight","volume":"93","author":"Br\u00f8ns","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613551583500_R4","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00125-005-1669-7","article-title":"Low birthweight is associated with specific changes in muscle insulin-signalling protein expression","volume":"48","author":"Ozanne","year":"2005","journal-title":"Diabetologia"},{"key":"2020071613551583500_R5","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1007\/s00125-006-0466-2","article-title":"Decreased protein levels of key insulin signalling molecules in adipose tissue from young men with a low birthweight: potential link to increased risk of diabetes?","volume":"49","author":"Ozanne","year":"2006","journal-title":"Diabetologia"},{"key":"2020071613551583500_R6","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/oby.2008.605","article-title":"Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter in newborns","volume":"17","author":"Gemma","year":"2009","journal-title":"Obesity (Silver Spring)"},{"key":"2020071613551583500_R7","doi-asserted-by":"crossref","first-page":"17046","DOI":"10.1073\/pnas.0806560105","article-title":"Persistent epigenetic differences associated with prenatal exposure to famine in humans","volume":"105","author":"Heijmans","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613551583500_R8","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1093\/hmg\/ddp353","article-title":"DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific","volume":"18","author":"Tobi","year":"2009","journal-title":"Hum Mol Genet"},{"issue":"Suppl","key":"2020071613551583500_R9","first-page":"31","article-title":"DNA methylation versus gene expression","volume":"83","author":"Bird","year":"1984","journal-title":"J Embryol Exp Morphol"},{"key":"2020071613551583500_R10","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1126\/science.1083557","article-title":"Chromosomal instability and tumors promoted by DNA hypomethylation","volume":"300","author":"Eden","year":"2003","journal-title":"Science"},{"key":"2020071613551583500_R11","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/321209a0","article-title":"CpG-rich islands and the function of DNA methylation","volume":"321","author":"Bird","year":"1986","journal-title":"Nature"},{"key":"2020071613551583500_R12","doi-asserted-by":"crossref","first-page":"10604","DOI":"10.1073\/pnas.0500398102","article-title":"Epigenetic differences arise during the lifetime of monozygotic twins","volume":"102","author":"Fraga","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613551583500_R13","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s00125-008-1018-8","article-title":"Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle","volume":"51","author":"Ro\u0308nn","year":"2008","journal-title":"Diabetologia"},{"key":"2020071613551583500_R14","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1172\/JCI30938","article-title":"Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle","volume":"117","author":"Ling","year":"2007","journal-title":"J Clin Invest"},{"key":"2020071613551583500_R15","doi-asserted-by":"crossref","first-page":"e1000602","DOI":"10.1371\/journal.pgen.1000602","article-title":"Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context","volume":"5","author":"Christensen","year":"2009","journal-title":"PLoS Genet"},{"key":"2020071613551583500_R16","doi-asserted-by":"crossref","first-page":"6570","DOI":"10.1073\/pnas.0401401101","article-title":"Erralpha and Gabpa\/b specify PGC-1\u03b1-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle","volume":"101","author":"Mootha","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613551583500_R17","doi-asserted-by":"crossref","first-page":"33588","DOI":"10.1074\/jbc.M507621200","article-title":"Peroxisome proliferator-activated receptor-\u03b3 co-activator 1\u03b1-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency","volume":"280","author":"Koves","year":"2005","journal-title":"J Biol Chem"},{"key":"2020071613551583500_R18","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/nature06613","article-title":"HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1\u03b1","volume":"451","author":"Arany","year":"2008","journal-title":"Nature"},{"key":"2020071613551583500_R19","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cell.2006.09.024","article-title":"Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators","volume":"127","author":"St-Pierre","year":"2006","journal-title":"Cell"},{"key":"2020071613551583500_R20","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00125-007-0916-5","article-title":"Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion","volume":"51","author":"Ling","year":"2008","journal-title":"Diabetologia"},{"key":"2020071613551583500_R21","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","article-title":"PGC-1\u03b1-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat Genet"},{"key":"2020071613551583500_R22","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1073\/pnas.1032913100","article-title":"Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1","volume":"100","author":"Patti","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613551583500_R23","doi-asserted-by":"crossref","first-page":"e6575","DOI":"10.1371\/journal.pone.0006575","article-title":"Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways","volume":"4","author":"Palsgaard","year":"2009","journal-title":"PLOS One"},{"key":"2020071613551583500_R24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.cmet.2009.07.011","article-title":"Non-CpG methylation of the PGC-1\u03b1 promoter through DNMT3B controls mitochondrial density","volume":"10","author":"Barre\u0300s","year":"2009","journal-title":"Cell Metab"},{"key":"2020071613551583500_R25","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1172\/JCI21889","article-title":"Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins","volume":"114","author":"Ling","year":"2004","journal-title":"J Clin Invest"},{"key":"2020071613551583500_R26","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3945\/ajcn.2009.28085","article-title":"Differential epigenomic and transcriptomic responses in subcutaneous adipose tissue between low and high responders to caloric restriction","volume":"91","author":"Bouchard","year":"2010","journal-title":"Am J Clin Nutr"},{"key":"2020071613551583500_R27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF03165964","article-title":"High fat diet-induced obesity modifies the methylation pattern of leptin promoter in rats","volume":"65","author":"Milagro","year":"2009","journal-title":"J Physiol Biochem"},{"key":"2020071613551583500_R28","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1093\/carcin\/11.12.2093","article-title":"Effects of a high fat diet on liver DNA methylation in rats exposed to N-nitrosodimethylamine","volume":"11","author":"Camus","year":"1990","journal-title":"Carcinogenesis"},{"key":"2020071613551583500_R29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01635589609514457","article-title":"Effects of dietary fat content on the metabolism of NNK and on DNA methylation induced by NNK","volume":"26","author":"el-Bayoumy","year":"1996","journal-title":"Nutr Cancer"},{"key":"2020071613551583500_R30","doi-asserted-by":"crossref","first-page":"15439","DOI":"10.1074\/jbc.M611214200","article-title":"Peroxisome proliferator activator receptor \u03b3 coactivator-1 expression is reduced in obesity: potential pathogenic role of saturated fatty acids and p38 mitogen-activated protein kinase activation","volume":"282","author":"Crunkhorn","year":"2007","journal-title":"J Biol Chem"},{"key":"2020071613551583500_R31","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.2337\/diabetes.54.7.1926","article-title":"A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle","volume":"54","author":"Sparks","year":"2005","journal-title":"Diabetes"},{"key":"2020071613551583500_R32","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2337\/diacare.28.1.151","article-title":"Altered fat tissue distribution in young adult men who had low birth weight","volume":"28","author":"Rasmussen","year":"2005","journal-title":"Diabetes Care"},{"key":"2020071613551583500_R33","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1113\/jphysiol.2009.169078","article-title":"Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men","volume":"587","author":"Br\u00f8ns","year":"2009","journal-title":"J Physiol"},{"key":"2020071613551583500_R34","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1007\/BF00400638","article-title":"Multiple defects of both hepatic and peripheral intracellular glucose processing contribute to the hyperglycaemia of NIDDM","volume":"38","author":"Vaag","year":"1995","journal-title":"Diabetologia"},{"key":"2020071613551583500_R35","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1093\/bioinformatics\/18.11.1427","article-title":"MethPrimer: designing primers for methylation PCRs","volume":"18","author":"Li","year":"2002","journal-title":"Bioinformatics"},{"key":"2020071613551583500_R36","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1093\/bioinformatics\/bth346","article-title":"Quantitative DNA methylation analysis based on four-dye trace data from direct sequencing of PCR amplificates","volume":"20","author":"Lewin","year":"2004","journal-title":"Bioinformatics"},{"key":"2020071613551583500_R37","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1056\/NEJM199710023371407","article-title":"Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging","volume":"337","author":"Weindruch","year":"1997","journal-title":"N Engl J Med"},{"key":"2020071613551583500_R38","doi-asserted-by":"crossref","first-page":"6107","DOI":"10.1073\/pnas.96.11.6107","article-title":"DNA methylation is a reversible biological signal","volume":"96","author":"Ramchandani","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613551583500_R39","doi-asserted-by":"crossref","first-page":"E607","DOI":"10.1152\/ajpendo.00729.2007","article-title":"Insulin-resistant muscle is exercise resistant: evidence for reduced response of nuclear-encoded mitochondrial genes to exercise","volume":"294","author":"De Filippis","year":"2008","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2020071613551583500_R40","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1038\/ng1909","article-title":"DNA methylation profiling of human chromosomes 6, 20 and 22","volume":"38","author":"Eckhardt","year":"2006","journal-title":"Nat Genet"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/95\/6\/3048\/9069847\/jcem3048.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/95\/6\/3048\/9069847\/jcem3048.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:57:30Z","timestamp":1594947450000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/95\/6\/3048\/2598922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,1]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010,6,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2009-2413","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,1]]}}}