title: A decrease in DKK1, a WNT inhibitor, contributes to placental lipid accumulation in an obesity-prone rat model.
abstract: 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.
authors: Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, Urbana, Illinois 61801, USA.
authors: Rita S
authors: RS
authors: Strakovsky
authors: Yuan-Xiang
authors: YX
authors: Pan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C531384:Dkk1 protein, rat; D005230:Fatty Acids, Nonesterified; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins