Maternal pregravid obesity changes gene expression profiles toward greater inflammation and reduced insulin sensitivity in umbilical cord

被引:28
作者
Thakali, Keshari M. [1 ,2 ]
Saben, Jessica [1 ,2 ]
Faske, Jennifer B. [1 ]
Lindsey, Forrest [1 ]
Gomez-Acevedo, Horacio [1 ,2 ]
Lowery, Curtis L., Jr. [3 ]
Badger, Thomas M. [1 ,2 ]
Andres, Aline [1 ,2 ]
Shankar, Kartik [1 ,2 ]
机构
[1] Arkansas Childrens Hosp, Arkansas Childrens Nutr Ctr, Little Rock, AR 72202 USA
[2] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA
[3] Univ Arkansas Med Sci, Dept Obstet & Gynecol, Little Rock, AR 72205 USA
基金
美国国家卫生研究院;
关键词
HIGH-FAT DIET; PREGNANCY; LEPTIN; METHYLATION; RESISTANCE; LIPOTOXICITY; ADIPOCYTES; ADIPOSITY; PROMOTER; GLUCOSE;
D O I
10.1038/pr.2014.72
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
BACKGROUND: Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC). METHODS: UCs from 12 lean (pregravid BMI < 24.9) and 10 overweight/obese (pregravid BMI >= 25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays. Metabolic parameters were assayed in mother's plasma and cord blood. RESULTS: Although offspring birth weight and adiposity (at 2 wk) did not differ between groups, expression of 232 transcripts was affected in UC from overweight/obese compared with those of lean mothers. Gene-set enrichment analysis revealed an upregulation of genes related to metabolism, stimulus and defense response, and inhibitory to insulin signaling in the overweight/obese group. We confirmed that EGR1, periostin, and FOSB mRNA expression was induced in UCs from overweight/obese mothers, while endothelin receptor B, KLF10, PEG3, and EGLN3 expression was decreased. Messenger RNA expression of EGR1, FOSB, MEST, and SOCS1 were positively correlated (P < 0.05) with mother's first-trimester body fat mass (%). CONCLUSION: Our data suggest a positive association between maternal obesity and changes in UC gene expression profiles favoring inflammation and insulin resistance, potentially predisposing infants to develop metabolic dysfunction later on in life.
引用
收藏
页码:202 / 210
页数:9
相关论文
共 40 条
[1]   New Emerging Potentials for Human Wharton's Jelly Mesenchymal Stem Cells: Immunological Features and Hepatocyte-Like Differentiative Capacity [J].
Anzalone, Rita ;
Lo Iacono, Melania ;
Corrao, Simona ;
Magno, Francesca ;
Loria, Tiziana ;
Cappello, Francesco ;
Zummo, Giovanni ;
Farina, Felicia ;
La Rocca, Giampiero .
STEM CELLS AND DEVELOPMENT, 2010, 19 (04) :423-438
[2]   Pregravid Obesity Associates With Increased Maternal Endotoxemia and Metabolic Inflammation [J].
Basu, Subhabrata ;
Haghiac, Maricela ;
Surace, Peter ;
Challier, Jean-Claude ;
Guerre-Millo, Michele ;
Singh, Katherine ;
Waters, Thaddeus ;
Minium, Judi ;
Presley, Larraine ;
Catalano, Patrick M. ;
Hauguel-de Mouzon, Sylvie .
OBESITY, 2011, 19 (03) :476-482
[3]   Maternal Obesity during Gestation Impairs Fatty Acid Oxidation and Mitochondrial SIRT3 Expression in Rat Offspring at Weaning [J].
Borengasser, Sarah J. ;
Lau, Franchesca ;
Kang, Ping ;
Blackburn, Michael L. ;
Ronis, Martin J. J. ;
Badger, Thomas M. ;
Shankar, Kartik .
PLOS ONE, 2011, 6 (08)
[4]   Transfer of insulin lispro across the human placenta - In vitro perfusion studies [J].
Boskovic, R ;
Feig, DS ;
Derewlany, L ;
Knie, B ;
Portnoi, G ;
Koren, G .
DIABETES CARE, 2003, 26 (05) :1390-1394
[5]   Fetuses of Obese Mothers Develop Insulin Resistance in Utero [J].
Catalano, Patrick M. ;
Presley, Larraine ;
Minium, Judi ;
Mouzon, Sylvie Hauguel-de .
DIABETES CARE, 2009, 32 (06) :1076-1080
[6]   Editorial: Obesity and pregnancy - The propagation of a viscous cycle? [J].
Catalano, PM .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (08) :3505-3506
[7]   Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta [J].
Challier, J. C. ;
Basu, S. ;
Bintein, T. ;
Minium, J. ;
Hotmire, K. ;
Catalano, P. M. ;
Mouzon, S. Hauguel-de .
PLACENTA, 2008, 29 (03) :274-281
[8]   Early growth response 1 (EGR1) A gene with as many names as biological functions [J].
DeLigio, J. Thomas ;
Zorio, Diego A. R. .
CANCER BIOLOGY & THERAPY, 2009, 8 (20) :1889-1892
[9]   Maternal Pregestational BMI Is Associated With Methylation of the PPARGC1A Promoter in Newborns [J].
Gemma, Carolina ;
Sookoian, Silvia ;
Alvarinas, Jorge ;
Garcia, Silvia I. ;
Quintana, Laura ;
Kanevsky, Diego ;
Gonzalez, Claudio D. ;
Pirola, Carlos J. .
OBESITY, 2009, 17 (05) :1032-1039
[10]   Epigenetic Gene Promoter Methylation at Birth Is Associated With Child's Later Adiposity [J].
Godfrey, Keith M. ;
Sheppard, Allan ;
Gluckman, Peter D. ;
Lillycrop, Karen A. ;
Burdge, Graham C. ;
McLean, Cameron ;
Rodford, Joanne ;
Slater-Jefferies, Joanne L. ;
Garratt, Emma ;
Crozier, Sarah R. ;
Emerald, B. Starling ;
Gale, Catharine R. ;
Inskip, Hazel M. ;
Cooper, Cyrus ;
Hanson, Mark A. .
DIABETES, 2011, 60 (05) :1528-1534