title: Maternal diabetes leads to unphysiological high lipid accumulation in rabbit preimplantation embryos.
abstract: According to the "developmental origin of health and disease" hypothesis, the metabolic set points of glucose and lipid metabolism are determined prenatally. In the case of a diabetic pregnancy, the embryo is exposed to higher glucose and lipid concentrations as early as during preimplantation development. We used the rabbit to study the effect of maternal diabetes type 1 on lipid accumulation and expression of lipogenic markers in preimplantation blastocysts. Accompanied by elevated triglyceride and glucose levels in the maternal blood, embryos from diabetic rabbits showed a massive intracellular lipid accumulation and increased expression of fatty acid transporter 4, fatty acid-binding protein 4, perilipin/adipophilin, and maturation of sterol-regulated element binding protein. However, expression of fatty acid synthase, a key enzyme for de novo synthesis of fatty acids, was not altered in vivo. During a short time in vitro culture of rabbit blastocysts, the accumulation of lipid droplets and expression of lipogenic markers were directly correlated with increasing glucose concentration, indicating that hyperglycemia leads to increased lipogenesis in the preimplantation embryo. Our study shows the decisive effect of glucose as the determining factor for fatty acid metabolism and intracellular lipid accumulation in preimplantation embryos.
authors.affiliation: Department of Anatomy and Cell Biology (M.S., M.P., S.S., J.G., E.H., J.M.K., B.F., An.N.S.) and Department of Cardiothoracic Surgery (Al.N.S.), Faculty of Medicine, Martin Luther University, 06097 Halle (Saale), Germany; and Department of Obstetrics and Gynaecology (T.P.), University Medical Center Groningen, University of Groningen, 9712 CP Groningen, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Schindler
authors.forename: Mareike
authors.initials: M
authors.lastname: Pendzialek
authors.forename: Alexander
authors.initials: A
authors.lastname: Navarrete Santos
authors.forename: Torsten
authors.initials: T
authors.lastname: Plösch
authors.forename: Stefanie
authors.initials: S
authors.lastname: Seyring
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Gürke
authors.forename: Elisa
authors.initials: E
authors.lastname: Haucke
authors.forename: Julia Miriam
authors.initials: JM
authors.lastname: Knelangen
authors.forename: Bernd
authors.initials: B
authors.lastname: Fischer
authors.forename: Anne Navarrete
authors.initials: AN
authors.lastname: Santos
mesh_terms: D000496:Alloxan / Q000737:chemistry; D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D008055:Lipids / Q000737:chemistry*; D011247:Pregnancy; D011248:Pregnancy Complications; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D011270:Pregnancy, Animal; D018075:RNA, Complementary / Q000378:metabolism; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D008055:Lipids; D018075:RNA, Complementary; D014280:Triglycerides; D000496:Alloxan