Prenatal ethanol exposure induces the osteoarthritis-like phenotype in female adult offspring rats with a post-weaning high-fat diet and its intrauterine programming mechanisms of cholesterol metabolism.
Fiche publication
Date publication
octobre 2015
Journal
Toxicology letters
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MAGDALOU Jacques
Tous les auteurs :
Ni Q, Wang L, Wu Y, Shen L, Qin J, Liu Y, Magdalou J, Chen L, Wang H
Lien Pubmed
Résumé
Osteoarthritis (OA) development is associated with hypercholesterolemia in adults. Our previous study demonstrated that offspring with intrauterine growth retardation (IUGR) due to prenatal ethanol exposure (PEE) had a high risk of developing hypercholesterolemia and metabolic syndrome when fed a post-weaning high-fat diet (HFD). In this study, we examined the changes in articular chondrocytes of IUGR offspring induced by PEE and explored its intrauterine programming mechanisms related to cholesterol metabolism. Using the PEE/IUGR model, serum and tibias from female fetuses and adult female offspring fed a post-weaning HFD were collected and examined for cholesterol metabolism and histology. The results showed that PEE adult offspring manifested significant catch-up growth. Their serum total cholesterol (TCH) and low-density lipoprotein-cholesterol increased and high-density lipoprotein-cholesterol decreased; the osteoarthritis-like phenotype and an increased TCH content were observed in articular cartilage; and the expression of insulin-like growth factor1 (IGF1) and cholesterol efflux pathway, including ATP-binding-cassette transporter A1 and liver X receptor, was reduced. The expression of IGF1 and cholesterol efflux pathway was also lower in the PEE fetuses. This study showed PEE could induce an enhanced susceptibility to HFD-induced OA in adult female IUGR offspring. The underlying mechanism related to cholesterol accumulation in cartilage mediated by intrauterine programming.
Mots clés
ATP Binding Cassette Transporter 1, metabolism, Age Factors, Animals, Body Weight, drug effects, Cartilage, drug effects, Cholesterol, Dietary, metabolism, Chondrocytes, drug effects, Diet, High-Fat, adverse effects, Ethanol, toxicity, Female, Fetal Growth Retardation, chemically induced, Insulin-Like Growth Factor I, metabolism, Liver X Receptors, Matrix Metalloproteinases, metabolism, Orphan Nuclear Receptors, metabolism, Osteoarthritis, chemically induced, Phenotype, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Wistar, Tibia, drug effects
Référence
Toxicol. Lett.. 2015 Oct 14;238(2):117-25