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Biol Reprod
2012 Mar 22;863:81. doi: 10.1095/biolreprod.111.094482.
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A decrease in DKK1, a WNT inhibitor, contributes to placental lipid accumulation in an obesity-prone rat model.
Strakovsky RS
,
Pan YX
.
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Placenta, as the sole transport mechanism between mother and fetus, links the maternal physical state and the immediate as well as lifelong outcomes of the offspring. The present study examined the consequences of maternal obesity on placental lipid accumulation and metabolism. Pregnant obesity-prone (OP) and obesity-resistant (OR) rat strains were fed a control diet throughout gestation. Placentas were collected on Gestational Day 21 for mRNA and oxidative stress analysis, and frozen placental sections were analyzed for fat accumulation as well as beta-catenin and Dickkopf homolog 1 (Xenopus laevis) (DKK1) localization. JEG3 trophoblast cells were cultured in vitro to determine the relationship between DKK1 and lipid accumulation. Maternal plasma and placental nonesterified fatty acids and triglycerides (TG) were elevated in OP dams. Placental Dkk1 mRNA content was 4-fold lower in OP placentas, and a significant increase was noted in beta-catenin accumulation as well as in mRNA content of fat transport and TG synthesis genes, including Ppard (peroxisome proliferator-activated receptor delta), Slc27a1 (fatty acid transport protein 1; also known as Fatp1), Cd36 (cluster of differentiation 36; also known as fatty acid translocation [Fat]), Lipin1, and Lipin3. Significant lipid accumulation was found within the decidual zones in OP, but not OR, placentas, and thickness of the decidual and junctional zones was significantly smaller in OP than in OR placentas. Overexpression of DKK1 in JEG3 cells decreased lipid accumulation and mRNA content of PPARD, SLC27A1, CD36, LIPIN1, and LIPIN3. Our results demonstrate that DKK1 is regulating certain aspects of placental lipid metabolism through the WNT signaling pathway.
Akyol,
Obesity induced by cafeteria feeding and pregnancy outcome in the rat.
2009, Pubmed
Akyol,
Obesity induced by cafeteria feeding and pregnancy outcome in the rat.
2009,
Pubmed
Alvino,
Maternal and fetal fatty acid profile in normal and intrauterine growth restriction pregnancies with and without preeclampsia.
2008,
Pubmed
Barker,
Fetal and placental size and risk of hypertension in adult life.
1990,
Pubmed
Boden,
Obesity and free fatty acids.
2008,
Pubmed
Brosens,
The role of the spiral arteries in the pathogenesis of preeclampsia.
1972,
Pubmed
Challier,
Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta.
2008,
Pubmed
Chang,
Metabolic differences between obesity-prone and obesity-resistant rats.
1990,
Pubmed
Chavez,
Lipid oversupply, selective insulin resistance, and lipotoxicity: molecular mechanisms.
2010,
Pubmed
Chen,
Activation of the Wnt pathway plays a pathogenic role in diabetic retinopathy in humans and animal models.
2009,
Pubmed
Cheng,
Wnt-1 signaling inhibits human umbilical vein endothelial cell proliferation and alters cell morphology.
2003,
Pubmed
Clegg,
Reduced anorexic effects of insulin in obesity-prone rats fed a moderate-fat diet.
2005,
Pubmed
Dash,
Trophoblast apoptosis is inhibited by hepatocyte growth factor through the Akt and beta-catenin mediated up-regulation of inducible nitric oxide synthase.
2005,
Pubmed
Douglas,
Vascular endothelial growth factor receptor 2 (VEGFR-2) functions to promote uterine decidual angiogenesis during early pregnancy in the mouse.
2009,
Pubmed
Duttaroy,
Fetal growth and development: roles of fatty acid transport proteins and nuclear transcription factors in human placenta.
2004,
Pubmed
Duttaroy,
Transport of fatty acids across the human placenta: a review.
2009,
Pubmed
Elchalal,
Insulin and fatty acids regulate the expression of the fat droplet-associated protein adipophilin in primary human trophoblasts.
2005,
Pubmed
Farley,
Feto-placental adaptations to maternal obesity in the baboon.
2009,
Pubmed
Galceran,
Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice.
1999,
Pubmed
Getsios,
Regulation of beta-catenin mRNA and protein levels in human villous cytotrophoblasts undergoing aggregation and fusion in vitro: correlation with E-cadherin expression.
2000,
Pubmed
Gorski,
Maternal obesity increases hypothalamic leptin receptor expression and sensitivity in juvenile obesity-prone rats.
2007,
Pubmed
Hannan,
Models for study of human embryo implantation: choice of cell lines?
2010,
Pubmed
He,
PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.
1999,
Pubmed
Heinonen,
Weights of placentae from small-for-gestational age infants revisited.
2001,
Pubmed
Hellerstedt,
The effects of cigarette smoking and gestational weight change on birth outcomes in obese and normal-weight women.
1997,
Pubmed
Herrera,
Maternal lipid metabolism and placental lipid transfer.
2006,
Pubmed
Hewitt,
Placental expression of secreted frizzled related protein-4 in the rat and the impact of glucocorticoid-induced fetal and placental growth restriction.
2006,
Pubmed
Huda,
Obesity in pregnancy: prevalence and metabolic consequences.
2010,
Pubmed
Ikeda,
In vitro approaches to evaluate placental drug transport by using differentiating JEG-3 human choriocarcinoma cells.
2011,
Pubmed
Ishikawa,
Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis.
2001,
Pubmed
,
Xenbase
Jackman,
Energy expenditure in obesity-prone and obesity-resistant rats before and after the introduction of a high-fat diet.
2010,
Pubmed
Ji,
Fasting plasma triglyceride levels and fat oxidation predict dietary obesity in rats.
2003,
Pubmed
Ji,
Reduced capacity for fatty acid oxidation in rats with inherited susceptibility to diet-induced obesity.
2007,
Pubmed
Ji,
Reduced hepatocyte fatty acid oxidation in outbred rats prescreened for susceptibility to diet-induced obesity.
2008,
Pubmed
Jones,
High-fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57/BL6 mice.
2009,
Pubmed
Katoh,
WNT signaling pathway and stem cell signaling network.
2007,
Pubmed
Kawano,
Secreted antagonists of the Wnt signalling pathway.
2003,
Pubmed
,
Xenbase
Levin,
Reduced central leptin sensitivity in rats with diet-induced obesity.
2002,
Pubmed
Levin,
Maternal obesity alters adiposity and monoamine function in genetically predisposed offspring.
2002,
Pubmed
Levin,
Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats.
2003,
Pubmed
Levin,
Differential effects of exercise on body weight gain and adiposity in obesity-prone and -resistant rats.
2006,
Pubmed
Levin,
Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats.
1997,
Pubmed
Liang,
High-saturated-fat diet induces gestational diabetes and placental vasculopathy in C57BL/6 mice.
2010,
Pubmed
Luquet,
Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes.
2005,
Pubmed
Madsen,
Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome.
2010,
Pubmed
Magnusson-Olsson,
Effect of maternal triglycerides and free fatty acids on placental LPL in cultured primary trophoblast cells and in a case of maternal LPL deficiency.
2007,
Pubmed
Marconi,
Lactacidemia in intrauterine growth restricted (IUGR) pregnancies: relationship to clinical severity, oxygenation and placental weight.
2006,
Pubmed
Matsuo,
Peroxisome proliferators and retinoids affect JEG-3 choriocarcinoma cell function.
1994,
Pubmed
Matsuzaki,
Overnourishing pregnant adolescent ewes preserves perirenal fat deposition in their growth-restricted fetuses.
2006,
Pubmed
McCurdy,
Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates.
2009,
Pubmed
Miao,
Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator.
2004,
Pubmed
Michel,
Stress facilitates body weight gain in genetically predisposed rats on medium-fat diet.
2003,
Pubmed
Monkley,
Targeted disruption of the Wnt2 gene results in placentation defects.
1996,
Pubmed
Nakano,
The cytoplasmic expression of E-cadherin and beta-catenin in bovine trophoblasts during binucleate cell differentiation.
2005,
Pubmed
Pardi,
Placental-fetal interrelationship in IUGR fetuses--a review.
2002,
Pubmed
Parr,
Wnt7b regulates placental development in mice.
2001,
Pubmed
Paulsen,
Characterization of beta-cell mass and insulin resistance in diet-induced obese and diet-resistant rats.
2010,
Pubmed
Peng,
Dickkopf-1 secreted by decidual cells promotes trophoblast cell invasion during murine placentation.
2008,
Pubmed
Pollheimer,
Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast.
2006,
Pubmed
Prestwich,
Wnt/beta-catenin signaling in adipogenesis and metabolism.
2007,
Pubmed
Pérez-Pérez,
Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells.
2009,
Pubmed
Rajasingam,
A prospective study of pregnancy outcome and biomarkers of oxidative stress in nulliparous obese women.
2009,
Pubmed
Rena,
Activation of beta-catenin signalling increases StarD7 gene expression in JEG-3 cells.
2009,
Pubmed
Roberts,
Effect of increasing maternal body mass index on oxidative and nitrative stress in the human placenta.
2009,
Pubmed
Schaiff,
Peroxisome proliferator-activated receptor-gamma and retinoid X receptor signaling regulate fatty acid uptake by primary human placental trophoblasts.
2005,
Pubmed
Seidell,
Obesity, insulin resistance and diabetes--a worldwide epidemic.
2000,
Pubmed
Smadja,
The Wnt antagonist Dickkopf-1 increases endothelial progenitor cell angiogenic potential.
2010,
Pubmed
Sonderegger,
Complex expression pattern of Wnt ligands and frizzled receptors in human placenta and its trophoblast subtypes.
2007,
Pubmed
Stewart,
Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers.
2007,
Pubmed
Taricco,
Foetal and placental weights in relation to maternal characteristics in gestational diabetes.
2003,
Pubmed
Tkacs,
Obesity-prone rats have preexisting defects in their counterregulatory response to insulin-induced hypoglycemia.
2004,
Pubmed
Tulac,
Identification, characterization, and regulation of the canonical Wnt signaling pathway in human endometrium.
2003,
Pubmed
Urban,
Concentration of free fatty acids (FFA) in amniotic fluid and maternal and cord serum in cases of intrauterine growth retardation.
1986,
Pubmed
White,
Expression of secreted frizzled-related protein 4 in the primate placenta.
2009,
Pubmed
Xu,
Effect of placental fatty acid metabolism and regulation by peroxisome proliferator activated receptor on pregnancy and fetal outcomes.
2007,
Pubmed