title: Maternal Obesity Programs Senescence Signaling and Glucose Metabolism in Osteo-Progenitors From Rat and Human.
abstract: Nutritional status during intrauterine and early postnatal life impacts the risk of chronic diseases, presumably via epigenetic mechanisms. However, evidence on the impact of gestational events on regulation of embryonic bone cell fate is sparse. We investigated the effects of maternal obesity on fetal osteoblast development in both rodents and humans. Female rats were fed control or an obesogenic high-fat diet (HFD) for 12 weeks and mated with male rats fed control diets, and respective maternal diets were continued during pregnancy. Embryonic rat osteogenic calvarial cells (EOCCs) were taken from gestational day 18.5 fetuses from control and HFD dams. EOCCs from HFD obese dams showed increases in p53/p21-mediated cell senescence signaling but decreased glucose metabolism. Decreased aerobic glycolysis in HFD-EOCCs was associated with decreased osteoblastic cell differentiation and proliferation. Umbilical cord human mesenchymal stem cells (MSCs) from 24 pregnant women (12 obese and 12 lean) along with placentas were collected upon delivery. The umbilical cord MSCs of obese mothers displayed less potential toward osteoblastogenesis and more towards adipogenesis. Human MSCs and placenta from obese mothers also exhibited increased cell senescence signaling, whereas MSCs showed decreased glucose metabolism and insulin resistance. Finally, we showed that overexpression of p53 linked increased cell senescence signaling and decreased glucose metabolism in fetal osteo-progenitors from obese rats and humans. These findings suggest programming of fetal preosteoblastic cell senescence signaling and glucose metabolism by maternal obesity.
authors.affiliation: Arkansas Children's Nutrition Center (J.-R.C., O.P.L., M.L.B., T.M.B., A.A., K.S.), Department of Pediatrics (J.-R.C., O.P.L., M.L.B., R.E.F., T.M.B., A.A., K.S.), University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute (S.R., R.E.F.), Little Rock, Arkansas 72202.
authors.forename: Jin-Ran
authors.initials: JR
authors.lastname: Chen
authors.affiliation: Arkansas Children's Nutrition Center (J.-R.C., O.P.L., M.L.B., T.M.B., A.A., K.S.), Department of Pediatrics (J.-R.C., O.P.L., M.L.B., R.E.F., T.M.B., A.A., K.S.), University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute (S.R., R.E.F.), Little Rock, Arkansas 72202.
authors.forename: Oxana P
authors.initials: OP
authors.lastname: Lazarenko
authors.affiliation: Arkansas Children's Nutrition Center (J.-R.C., O.P.L., M.L.B., T.M.B., A.A., K.S.), Department of Pediatrics (J.-R.C., O.P.L., M.L.B., R.E.F., T.M.B., A.A., K.S.), University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute (S.R., R.E.F.), Little Rock, Arkansas 72202.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blackburn
authors.affiliation: Arkansas Children's Nutrition Center (J.-R.C., O.P.L., M.L.B., T.M.B., A.A., K.S.), Department of Pediatrics (J.-R.C., O.P.L., M.L.B., R.E.F., T.M.B., A.A., K.S.), University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute (S.R., R.E.F.), Little Rock, Arkansas 72202.
authors.forename: Shannon
authors.initials: S
authors.lastname: Rose
authors.affiliation: Arkansas Children's Nutrition Center (J.-R.C., O.P.L., M.L.B., T.M.B., A.A., K.S.), Department of Pediatrics (J.-R.C., O.P.L., M.L.B., R.E.F., T.M.B., A.A., K.S.), University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute (S.R., R.E.F.), Little Rock, Arkansas 72202.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Frye
authors.affiliation: Arkansas Children's Nutrition Center (J.-R.C., O.P.L., M.L.B., T.M.B., A.A., K.S.), Department of Pediatrics (J.-R.C., O.P.L., M.L.B., R.E.F., T.M.B., A.A., K.S.), University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute (S.R., R.E.F.), Little Rock, Arkansas 72202.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
authors.affiliation: Arkansas Children's Nutrition Center (J.-R.C., O.P.L., M.L.B., T.M.B., A.A., K.S.), Department of Pediatrics (J.-R.C., O.P.L., M.L.B., R.E.F., T.M.B., A.A., K.S.), University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute (S.R., R.E.F.), Little Rock, Arkansas 72202.
authors.forename: Aline
authors.initials: A
authors.lastname: Andres
authors.affiliation: Arkansas Children's Nutrition Center (J.-R.C., O.P.L., M.L.B., T.M.B., A.A., K.S.), Department of Pediatrics (J.-R.C., O.P.L., M.L.B., R.E.F., T.M.B., A.A., K.S.), University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute (S.R., R.E.F.), Little Rock, Arkansas 72202.
authors.forename: Kartik
authors.initials: K
authors.lastname: Shankar
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012886:Skull / Q000166:cytology; D045162:Thiazolidinediones / Q000494:pharmacology; D013851:Thinness / Q000378:metabolism / Q000503:physiopathology
chemical_list: D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005947:Glucose