Glucoseandlipidmetabolismdisorderinolanzapine-inducedobesityratsanditsinfluencingmechanism

Abstract:

Objective：Toinvestigatethedisorderofglucoseandlipidmetabolisminducedbyolanzapineinratsanditsinfluencingmechanism.Methods：Accordingtotherandomdigitstablemethod，40healthyadultmaleratsweredividedintothecontrolgroupandtheobservationgroup，with20ratsineachgroup.Ratsinthecontrolgroupwerereceivednormalfood，whileintheobservationgroupwerefedwitholanzapine（1.2mg/kg）onthebasisofnormalfoodforcontinuousfourweeks.Afterfourweeks，indicatorchangesofbodyweight，glycemiaandlipidemiawerecompared.Additionally，pancreaticglycometabolismkeykinaseofglucokinase（GCK）andglucosetransporter-2（GLUT-2），andlipocyteskeykinaseofperoxisomeproliferatoractivatedreceptor-γ（PPARγ）andfattyacidsynthase（FAS）weremeasured.Results：Afterfourweeks，theweightofratsintheobservationgroupwas23%higherthanthatinthecontrolgroup，andtheweightofratsintheobservationgroupwassignificantlyhigherthanthatinthecontrolgroupfromthesecondweek（P<0.05）；fastingglucose，totalcholesterol，triglycerideandlowdensitylipoprotein（LDL）ofratsintheobservationgroupweresignificantlyhigherthanthoseinthecontrolgroup（P<0.05），butthehighdensitylipoprotein（HDL）ofratsintheobservationgroupwaslowerthanthatinthecontrolgroup（P<0.05）.ThemRNAexpressionlevelsofGCKandGLUT-2intheobservationgroupweresignificantlylowerthanthoseinthecontrolgroup（P<0.05），whilethemRNAexpressionlevelsofPPARγandFASgenesweresignifi－cantlyhigherthanthoseinthecontrolgroup（P<0.05）.Conclusion：Olanzapinecaninducethedisorderofglucoseandlipidmetabolisminrats，anditsmechanismmayberelatedtothedownregulatingkeyglycometabolicgenesofGCKandGLUT-2，andtheupregulatinglipocytesdifferentiationkeygenesofPPARγandFAS.