Early Hypothalamic FTO Overexpression in Response to Maternal Obesity – Potential Contribution to Postweaning Hyperphagia 英文参考文献.docVIP

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Early Hypothalamic FTO Overexpression in Response to Maternal Obesity – Potential Contribution to Postweaning Hyperphagia 英文参考文献.doc

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Early Hypothalamic FTO Overexpression in Response to Maternal Obesity – Potential Contribution to Postweaning Hyperphagia 英文参考文献

EarlyHypothalamicFTOOverexpressioninResponseto MaternalObesity–PotentialContributionto PostweaningHyperphagia VanniCaruso1,HuiChen1,2,MargaretJ.Morris1* 1Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia, 2School of Medical and Molecular Bioscience,FacultyofScience,UniversityofTechnology,Sydney,NewSouthWales,Australia Abstract Background:Intrauterineandpostnatalovernutritionprogramhyperphagia,adiposityandglucoseintoleranceinoffspring. Single-nucleotidepolymorphisms(SNPs)ofthefatmassandobesityassociated(FTO)genehavebeenlinkedtoincreased riskofobesity.FTOishighlyexpressedinhypothalamicregionscriticalforenergybalanceandhyperphagicphenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolicfunction,weinvestigatedtheimpactofmaternalobesityonFTO. Methods:FemaleSpragueDawleyratswereexposedtochoworhighfatdiet(HFD)for5weeksbeforemating,throughout gestationandlactation.Onpostnatalday1(PND1),somelitterswereadjustedto3pups(vs.12control)toinducepostnatal overnutrition.AtPND20,ratswereweanedontochoworHFDfor15weeks.FTOmRNAexpressioninthehypothalamusand liver,aswellashepaticmarkersoflipidmetabolismweremeasured. Results:Atweaning,hypothalamicFTOmRNAexpressionwasincreasedsignificantlyinoffspringofobesemothersandFTO was correlated with both visceral and epididymal fat mass (P,0.05); body weight approached significance (P=0.07). Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. PostnatalHFDfeedingsignificantlyreducedhepaticCarnitinePalmitoyltransferase-1abutdidnotaffecttheexpressionof otherhepaticmarkersinvestigated.FTOwasnotaffectedbychronicHFDfeeding. Significance: Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early