Excess of the endocannabinoid anandamide during lactation induces overweight, fat accumulation and insulin resistance in adult mice.docVIP

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Excess of the endocannabinoid anandamide during lactation induces overweight, fat accumulation and insulin resistance in adult mice.doc

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Excess of the endocannabinoid anandamide during lactation induces overweight, fat accumulation and insulin resistance in adult mice

Aguirreetal.DiabetologyMetabolicSyndrome2012,4:35 /content/4/1/35 DIABETOLOGY METABOLIC SYNDROME RESEARCH OpenAccess Excessoftheendocannabinoidanandamide duringlactationinducesoverweight,fat accumulationandinsulinresistanceinadultmice CarolinaAAguirre*,ValeskaACastilloandMiguelNLlanos Abstract Background:Environmentalconditionsinearlylifecaninducepermanentphysiologicalchanges,sometimes increasingtheriskofchronicdiseasesduringadulthood.Neuralandperipheralcircuitscontrollingenergybalance maybemodulatedduringsuchacriticalperiod.Sincetype1cannabinoidreceptors(CB1R)haverecentlyemerged astargetsformodulatingenergybalance,theirprematurechronicactivationduringearlylifemayresultinlong- termmetabolicconsequencesassociatedtooverweight/obesity.EndogenousactivationofCB1Rmainlyoccursafter bindingtotheendocannabinoidAnandamide(AEA). Objective:Toevaluatelong-termeffectsofAEAtreatmentduringlactationonbodyweight,epididymalfat accumulationandrelatedmetabolicparametersduringadulthood. Design:MalemicepupswereorallytreatedwithasolutionofAEA(20μg/gbodyweightinsoyoil)orvehicle duringthewholelactationperiod.Afterweaning,foodintakeandbodyweightwererecordedevery10days.Adult animalsweresubjectedtoglucoseandinsulintolerancetests.Subsequently,animalsweresacrificedand epididymalfatpadswereextracted.Circulatinglevelsofplasmainsulin,leptin,non-sterifiedfattyacids(NEFA), triglycerideandcholesterolwerealsoevaluated. Results:AEA-treatedmiceduringlactationshowedasignificantincreaseinaccumulatedfoodintake,bodyweight andepididymalfatduringadulthoodwhencomparedtocontrolmice.WhenevaluatingCB1Rproteinexpressionin epididymalfat,theAEA-treatedgroupshoweda150%increaseinexpressioncomparedtothecontrolmice.This groupalsodisplayedsignificantlyhigherlevelsofcirculatingglucose,insulin,leptin,triglycerides,cholesteroland NEFA.Moreover,amarkedstateofinsulinresistancewasanimportantfindingintheAEA-treatedgroup. Conclusion:Thisstudyshowedthatoverweight,accumulationofvisceralfatandassociatedmetabolic disturbances,such