Epigenetic programming of adipose-derived stem cells in low birthweight individuals

被引：33

作者：

Broholm, Christa ^{[1
]}

Olsson, Anders H. ^{[1
]}

Perfilyev, Alexander ^{[2
]}

Hansen, Ninna S. ^{[1
,3
]}

Schrolkamp, Maren ^{[1
]}

Strasko, Klaudia S. ^{[1
]}

Scheele, Camilla ^{[3
,4
]}

Ribel-Madsen, Rasmus ^{[1
,5
]}

Mortensen, Brynjulf ^{[6
]}

Jorgensen, Sine W. ^{[6
]}

Ling, Charlotte ^{[2
]}

Vaag, Allan ^{[1
,3
,6
]}

机构：

[1] Rigshosp, Dept Endocrinol Diabet & Metab, Sect 7652,Tagensvej 20, DK-2200 Copenhagen, Denmark

[2] Lund Univ, Dept Clin Sci Epigenet & Diabet, Ctr Diabet, CRC, Malmo, Sweden

[3] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark

[4] Rigshosp, Ctr Inflammat & Metab, Copenhagen, Denmark

[5] Danish Diabet Acad, Odense, Denmark

[6] Steno Diabet Ctr AS, Gentofte, Denmark

来源：

DIABETOLOGIA | 2016年 / 59卷 / 12期

关键词：

Adipocytes; Adipogenesis; Adipose tissue; Cyclin T2; Epigenetics; Fetal programming; Low birthweight; Metabolic disease; Type; 2; diabetes; YOUNG MEN BORN; DNA METHYLATION; GENE-EXPRESSION; CYCLIN T2; MUSCLE; METABOLISM; PPARGC1A; INSIGHTS; GLUCOSE; IMPACT;

D O I：

10.1007/s00125-016-4099-9

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Low birthweight (LBW) is associated with dysfunctions of adipose tissue and metabolic disease in adult life. We hypothesised that altered epigenetic and transcriptional regulation of adipose-derived stem cells (ADSCs) could play a role in programming adipose tissue dysfunction in LBW individuals. ADSCs were isolated from the subcutaneous adipose tissue of 13 normal birthweight (NBW) and 13 LBW adult men. The adipocytes were cultured in vitro, and genome-wide differences in RNA expression and DNA methylation profiles were analysed in ADSCs and differentiated adipocytes. We demonstrated that ADSCs from LBW individuals exhibit multiple expression changes as well as genome-wide alterations in methylation pattern. Reduced expression of the transcription factor cyclin T2 encoded by CCNT2 may play a key role in orchestrating several of the gene expression changes in ADSCs from LBW individuals. Indeed, silencing of CCNT2 in human adipocytes decreased leptin secretion as well as the mRNA expression of several genes involved in adipogenesis, including MGLL, LIPE, PPARG, LEP and ADIPOQ. Only subtle genome-wide mRNA expression and DNA methylation changes were seen in mature cultured adipocytes from LBW individuals. Epigenetic and transcriptional changes in LBW individuals are most pronounced in immature ADSCs that in turn may programme physiological characteristics of the mature adipocytes that influence the risk of metabolic diseases. Reduced expression of CCNT2 may play a key role in the developmental programming of adipose tissue.

引用

页码：2664 / 2673

页数：10

共 41 条

[1]

Increased rate of whole body lipolysis before and after 9 days of bed rest in healthy young men born with low birth weight [J].

Alibegovic, A. C. ;

Hojbjerre, L. ;

Sonne, M. P. ;

van Hall, G. ;

Alsted, T. J. ;

Kiens, B. ;

Stallknecht, B. ;

Dela, F. ;

Vaag, A. .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2010, 298 (03) :E555-E564

[2]

CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[3]

BERGSTROM J, 1975, SCAND J CLIN LAB INV, V35, P606

[4]

Analysis of the effect of natural sequence variation in Tat and in cyclin T on the formation and RNA binding properties of Tat-cyclin T complexes [J].

Bieniasz, PD ;

Grdina, TA ;

Bogerd, HP ;

Cullen, BR .

JOURNAL OF VIROLOGY, 1999, 73 (07) :5777-5786

[5]

Deoxyribonucleic Acid Methylation and Gene Expression of PPARGC1A in Human Muscle Is Influenced by High-Fat Overfeeding in a Birth-Weight-Dependent Manner [J].

Brons, Charlotte ;

Jacobsen, Stine ;

Nilsson, Emma ;

Ronn, Tina ;

Jensen, Christine B. ;

Storgaard, Heidi ;

Poulsen, Pernille ;

Groop, Leif ;

Ling, Charlotte ;

Astrup, Arne ;

Vaag, Allan .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2010, 95 (06) :3048-3056

[6]

Programming differentiation potential in mesenchymal stem cells [J].

Collas, Philippe .

EPIGENETICS, 2010, 5 (06) :476-482

[7]

Large-scale association analysis identifies new risk loci for coronary artery disease [J].

Deloukas, Panos ;

Kanoni, Stavroula ;

Willenborg, Christina ;

Farrall, Martin ;

Assimes, Themistocles L. ;

Thompson, John R. ;

Ingelsson, Erik ;

Saleheen, Danish ;

Erdmann, Jeanette ;

Goldstein, Benjamin A. ;

Stirrups, Kathleen ;

Koenig, Inke R. ;

Cazier, Jean-Baptiste ;

Johansson, Asa ;

Hall, Alistair S. ;

Lee, Jong-Young ;

Willer, Cristen J. ;

Chambers, John C. ;

Esko, Tonu ;

Folkersen, Lasse ;

Goel, Anuj ;

Grundberg, Elin ;

Havulinna, Aki S. ;

Ho, Weang K. ;

Hopewell, Jemma C. ;

Eriksson, Niclas ;

Kleber, Marcus E. ;

Kristiansson, Kati ;

Lundmark, Per ;

Lyytikainen, Leo-Pekka ;

Rafelt, Suzanne ;

Shungin, Dmitry ;

Strawbridge, Rona J. ;

Thorleifsson, Gudmar ;

Tikkanen, Emmi ;

Van Zuydam, Natalie ;

Voight, Benjamin F. ;

Waite, Lindsay L. ;

Zhang, Weihua ;

Ziegler, Andreas ;

Absher, Devin ;

Altshuler, David ;

Balmforth, Anthony J. ;

Barroso, Ines ;

Braund, Peter S. ;

Burgdorf, Christof ;

Claudi-Boehm, Simone ;

Cox, David ;

Dimitriou, Maria ;

Do, Ron .

NATURE GENETICS, 2013, 45 (01) :25-U52

[8]

Maternal nutrition at conception modulates DNA methylation of human metastable epialleles [J].

Dominguez-Salas, Paula ;

Moore, Sophie E. ;

Baker, Maria S. ;

Bergen, Andrew W. ;

Cox, Sharon E. ;

Dyer, Roger A. ;

Fulford, Anthony J. ;

Guan, Yongtao ;

Laritsky, Eleonora ;

Silver, Matt J. ;

Swan, Gary E. ;

Zeisel, Steven H. ;

Innis, Sheila M. ;

Waterland, Robert A. ;

Prentice, Andrew M. ;

Hennig, Branwen J. .

NATURE COMMUNICATIONS, 2014, 5

[9]

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk [J].

Dupuis, Josee ;

Langenberg, Claudia ;

Prokopenko, Inga ;

Saxena, Richa ;

Soranzo, Nicole ;

Jackson, Anne U. ;

Wheeler, Eleanor ;

Glazer, Nicole L. ;

Bouatia-Naji, Nabila ;

Gloyn, Anna L. ;

Lindgren, Cecilia M. ;

Magi, Reedik ;

Morris, Andrew P. ;

Randall, Joshua ;

Johnson, Toby ;

Elliott, Paul ;

Rybin, Denis ;

Thorleifsson, Gudmar ;

Steinthorsdottir, Valgerdur ;

Henneman, Peter ;

Grallert, Harald ;

Dehghan, Abbas ;

Hottenga, Jouke Jan ;

Franklin, Christopher S. ;

Navarro, Pau ;

Song, Kijoung ;

Goel, Anuj ;

Perry, John R. B. ;

Egan, Josephine M. ;

Lajunen, Taina ;

Grarup, Niels ;

Sparso, Thomas ;

Doney, Alex ;

Voight, Benjamin F. ;

Stringham, Heather M. ;

Li, Man ;

Kanoni, Stavroula ;

Shrader, Peter ;

Cavalcanti-Proenca, Christine ;

Kumari, Meena ;

Qi, Lu ;

Timpson, Nicholas J. ;

Gieger, Christian ;

Zabena, Carina ;

Rocheleau, Ghislain ;

Ingelsson, Erik ;

An, Ping ;

O'Connell, Jeffrey ;

Luan, Jian'an ;

Elliott, Amanda .

NATURE GENETICS, 2010, 42 (02) :105-U32

[10]

Intrauterine programming of adult body composition [J].

Gale, CR ;

Martyn, CN ;

Kellingray, S ;

Eastell, R ;

Cooper, C .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (01) :267-272

← 1 2 3 4 5 →