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1、L.Martini(Eds.)ProgressinBrainResearch,Vol.181ISSN:0079-6123CopyrightÓ2010ElsevierB.V.Allrightsreserved.CHAPTER2Neuroendocrinecontrolofenergyhomeostasis:updateonnewinsights1,2SatyaP.KalraandPushpaS.Kalra1DepartmentofNeuroscience,McKnightBrainInstitute,CollegeofMedicine,Uni
2、versityofFlorida,Gainesville,Florida,UnitedStates2DepartmentofPhysiologyandFunctionalGenomics,McKnightBrainInstitute,CollegeofMedicine,UniversityofFlorida,Gainesville,Florida,UnitedStatesAbstract:Recentupsurgeinresearchhasuncovereddistinctcircuitriesthatregulateappetite,ene
3、rgyexpenditureandfataccrualunderthesupervisionofhormonalfeedbacksignallingofadipocyteleptinandgastricghrelininthehypothalamicintegrationofenergyhomeostasis.Ahostofmessengermoleculesofdiversechemicalcompositionandoriginmediatethecrosstalkbetweenthethreecircuitries.Leptinisno
4、wrecognizedasthemandatoryafferentsignalinmaintenanceofweighthomeostasis.Leptininsufficiencyinthehypothalamusduetodiminishedtransportofleptinacrosstheblood–brainbarrier(BBB)imposedbyenvironmentalcauses,suchasconsumptionofenergy-enricheddietsanddiminishedenergyexpenditure,orc
5、hestratesunregulatedfataccrualandtheattendantdiseaseclusterofmetabolicsyndrome.Bioavailabilityofleptinselectivelyinthehypothalamictargetswiththeaidofgenetherapysuccessfullyavertedtheenvironmentallyinducedmetabolicafflictionsandnormalizedlifespan.Thus,sustenanceofoptimalsuff
6、iciencyinleptinsignallingsolelyinthehypothalamusisanovelstrategytocombattheworldwideepidemicofobesityandmetabolicsyndrome.Keywords:appetite;energyexpenditure;fataccrual;leptin;hypothalamusIntroductioninsomepatients.Indeed,experimentalevidenceinthe1940sand1950sthatelectrolyt
7、iclesionsintheThecauseandeffectrelationshipbetweennutri-ventromedialhypothalamus(VMH)elicitedrelent-tion,energyimbalanceandhumanhealthhaslesshyperphagia,weightgainandmorbidobesity,beenappreciatedsincetimeimmemorial(Bray,whereaslesionsinthelateralhypothalamus(LH)1998;Kalraan
8、dKalra,2005).Therapeuticstrate-conferredimmobility,aphagiaandwasting,ledtogiesadap
