71: Pioglitazone therapy in offspring exposed to maternal obesity

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DIABETESAbstracts 71 78Moderators: Thomas Moore, MD; Yvonne Chang, MD71 Pioglitazone therapy in offspringexposed to maternal obesityArshag Kalanderian1, Nicola Abate2, Igor Patrikeev3, MonicaLongo1, Massoud Motamedi3, George R. Saade1, Egle Bytautiene11The University of TexasMedical Branch, Obstetrics &Gynecology,Galveston, TX, 2The University of TexasMedical Branch, InternalMedicine, Galveston, TX, 3The University of TexasMedicalBranch, Center for Biomedical Engineering, Galveston, TXOBJECTIVE: Pioglitazone(PL),ananti-diabeticdrugofthethiazolidinedionefamily, improvesglucoseandlipidmetabolisminthemuscles,adiposetissue,and liver by increasing insulin sensitivity via peroxisome proliferator-acti-vated receptorgamma(PPAR) activation.PPARmRNAexpression is in-creased in adipose tissue fromoffspringborn toobesemothers.Wehypoth-esize that activation of PPAR receptors by PL will improve the metabolicstatus of the offspring exposed tomaternal obesity in a previously validatedmousemodel of the fetal origin ofmetabolic syndrome.STUDY DESIGN: CD-1mice were placed on high fat diet for 3months priorto, and during pregnancy. The resulting pups were weaned to regular diet.Pupswererandomlyassignedtoreceive40mg/kgofPLbyoralgavagein0.5%ofmethyl cellulose (PL group, n10), or the same amount of 0.5%methylcellulose (CTR group, n8). Treatment was given once daily from10 to 12weeksofage.Immediatelybeforeandafterthetreatmentperiod,theoffspringwereweighed, their visceral adipose tissue (VAT)was evaluated using com-puted-tomography, bloodwas collected for fastingglucose (GL) and triglyc-eride(TRG)analysis,andintraperitonealglucosetolerance(IGTT)testswereperformed. Data was analyzed as change frompre-treatment using Studentt-test (significance: P0.05).RESULTS: PL therapy significantly attenuated the increase in bodyweight (BW) seen in the control mice (mean increase: PL 1.25% vs.CTR9.56%; Figure, P0.02). TRG levels increased by 15% in theCTRvs a 24% decrease in PL (Figure, P0.004). There was also a trendtowards lowerVAT and improvement inGL (fasting and IGTT) levelsin the offspring that received PL.CONCLUSION: Short therapy with PL in the offspring of obese mothersmitigates the weight and metabolic changes associated with develop-mental programming.Our data are novel and propose a potential rolefor drugs that activate PPAR receptors in the prevention of meta-bolic syndrome in adult offspring of obese mothers.72 Oral treatment with anti-oxidant N-acetylcysteinereduces maternal diabetes-inducedembryonic neural tube defectsYuanning Cao1, Zhiyong Zhao2, E. Albert Reece21University ofMaryland School ofMedicine, Department of Obstetrics,Gynecology, and Reproductive Sciences, Baltimore,MD, 2University ofMaryland School ofMedicine, Obstetrics, Gynecology & ReproductiveSciences and Biochemistry &Molecular Biology, Baltimore,MDOBJECTIVE: We and others have shown thatmaternal diabetes inducesembryonic malformations, including neural tube defects (NTDs), byincreasing oxidative and endoplasmic reticulum (ER) stress. The aimsof this study are to explore antioxidative approaches, using antioxi-dant N-acetylcysteine (NAC), to reduce NTDs and investigate theunderlying mechanisms.STUDY DESIGN: Diabetes mellitus in female mice was induced by in-travenous injection of streptozotocin (60mg/kg), before beingmatedwith normal male mice At embryonic day (E) 7.5, the mice weretreated with NAC (100 mg/kg, b.i.d) or vehicle through oral gavagefeeding for 3 days. At E10.5, the embryos were examined and neuraltube tissues were collected for protein assays.RESULTS: NAC treatment significantly reduced NTD rate in the em-bryos of diabetic mice (2.5%), compared with that in vehicle-treatedgroup (17.8%). Oxidative stress in the neural tubes was alleviated byNAC treatment, indicated by decreased levels of oxidative stressmarkers, 3-nitrotyrosine and 4-hydroxynonenal. In addition, the lev-els of ER stress factors (CHOP, calreticulin, p-PERK, and p-eIF2),which are increased in the embryos, were significantly reduced byNAC treatment.CONCLUSION: Pharmacological treatment with NAC ameliorates oxi-dative stress and reduces NTDs in the embryos of diabetic mice. Theantioxidant effects are associated with reduction in ER stress.73 In utero exposure to maternal obesityprograms offspring insulin resistanceMina Desai1, Diana Wolfe1, Thomas Magee1, Michael Ross11LABioMed at Harbor-UCLAMed. Ctr., Obstetricsand Gynecology, Torrance, CAOBJECTIVE: Epidemiological studies and animal models confirm thedevelopmental origins of obesity. Offspring born to obese or diabeticmothers are often larger at birth, and show increased adipose tissuemass and obesity and diabetes risk in later life. As the prevalence ofobesity among pregnant women continues to rise, increasing numberof children are exposed to an obese intrauterine environment duringdevelopment. We investigated whether exposure to maternal obesityduring pregnancy impacts on obesity and diabetes in the offspring.STUDY DESIGN: Rats were fed a high fat (HF; 60% k/cal) or control diet(10% k/cal) prior to and thoughout pregnancy. At 1 day of age, bloodwas collected from pups. Offspring litter size was standardized, andboth HF and Control offspring were cross-fostered and nursed byOral Concurrent Session 7 www.AJOG.orgSaturday, February 11, 2012 8:00 am 10:00 am LandmarkB,DallasHyatt RegencyS46 American Journal of Obstetrics& Gynecology Supplement to JANUARY 2012

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