2007
Enhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation
Plum L, Rother E, Münzberg H, Wunderlich FT, Morgan DA, Hampel B, Shanabrough M, Janoschek R, Könner AC, Alber J, Suzuki A, Krone W, Horvath TL, Rahmouni K, Brüning JC. Enhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation. Cell Metabolism 2007, 6: 431-445. PMID: 18054313, DOI: 10.1016/j.cmet.2007.10.012.Peer-Reviewed Original ResearchConceptsWhite adipose tissueSympathetic nerve activityBrown adipose tissuePI3k activationAdipose tissueLeptin-deficient ob/obOb/ob miceUnaltered body weightEnergy expenditureOb/obLeptin-sensitive neuronsNerve activityEndogenous leptinOb miceBody weightUCP1 expressionWAT morphologyEnergy homeostasisLeptinSkeletal muscleMicePTEN ablationSignaling pathwaysMitochondrial contentDirect genetic evidence
2006
Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity
Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Münzberg H, Shanabrough M, Burdakov D, Rother E, Janoschek R, Alber J, Belgardt BF, Koch L, Seibler J, Schwenk F, Fekete C, Suzuki A, Mak TW, Krone W, Horvath TL, Ashcroft FM, Brüning JC. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. Journal Of Clinical Investigation 2006, 116: 1886-1901. PMID: 16794735, PMCID: PMC1481658, DOI: 10.1172/jci27123.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChromonesDietEatingFemaleHypoglycemic AgentsHypothalamusInsulinLeptinMaleMembrane PotentialsMiceMice, KnockoutMorpholinesNeuronsObesityPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoinositide-3 Kinase InhibitorsPotassium ChannelsPro-OpiomelanocortinPTEN PhosphohydrolaseSecond Messenger SystemsTolbutamideConceptsPOMC neuronsATP-sensitive potassium channel activityBasal firing rateHypothalamic proopiomelanocortin (POMC) neuronsElectrical activityKATP channel activationPI3K inhibitor LY294002PTEN knockout micePotassium channel activityK inhibitor LY294002PI3K pathwayProopiomelanocortin neuronsHypothalamic receptorsICV administrationFood intakeKATP channelsKnockout miceMelanocortin systemLeptinFiring rateNeuronsMiceSTAT3 phosphorylationK pathwayInhibitor LY294002