Modulation of Cholesterol Transport by Insulin-Treated Gestational Diabetes Mellitus in Human Full-Term Placenta1
Autor: | Julie Lafond, Evemie Dubé, Maude Ethier-Chiasson |
---|---|
Rok vydání: | 2013 |
Předmět: |
medicine.medical_specialty
biology Cholesterol PCSK9 nutritional and metabolic diseases Very Low-Density Lipoprotein Receptor Cell Biology General Medicine medicine.disease Gestational diabetes chemistry.chemical_compound Endocrinology Reproductive Medicine chemistry Internal medicine LDL receptor biology.protein medicine lipids (amino acids peptides and proteins) Apolipoprotein A1 Liver X receptor Lipoprotein |
Zdroj: | Biology of Reproduction. 88 |
ISSN: | 1529-7268 0006-3363 |
DOI: | 10.1095/biolreprod.112.105619 |
Popis: | Gestational diabetes mellitus (GDM) is a common complication of pregnancy that is characterized by glucose intolerance, leads to dyslipidemia, and is aggravated by obesity. Cholesterol is taken up by the placenta as part of lipoproteins through the scavenger receptor class B type I receptor (SRBI), low-density lipoprotein receptor (LDLR), and very low density lipoprotein receptor (VLDLR), and its efflux is then mediated by ABCA1 and ABCG1. PCSK9 is involved in the degradation of LDLR and VLDLR. The goal of this study was to evaluate the impact of GDM and prepregnancy body mass index (BMI) on cholesterol transport through the modulation of the expression of several key players. Human full-term placenta, maternal, and venous cord blood samples were obtained at delivery from normal-weight women without GDM (n = 10), normal-weight women with GDM (n = 6), and overweight/obese women with GDM (n = 6). Lipids (total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, free fatty acids, apolipoprotein A1, apolipoprotein B100) levels were evaluated in blood samples. Messenger RNA and protein expression levels (LDLR, VLDLR, SRBI, ABCA1, ABCG1, proprotein convertase subtilisin/kexin type 9, liver x receptors, peroxisome proliferator-activated receptors) were assessed in human full-term placenta, respectively, by real-time RT-PCR and Western blots. Lipoprotein lipase activity was evaluated using a commercial kit on tissue homogenates. Overall, our study demonstrates that GDM affects the maternal and neonatal lipid profiles as well as different key players of placental cholesterol transfer from the maternal to the fetal circulation, depending on the maternal BMI. These changes could affect the fetal metabolism and predispose the fetus to future metabolic diseases. |
Databáze: | OpenAIRE |
Externí odkaz: |