2023
Preclinical, randomized phase 1, and compassionate use evaluation of REGN4461, a leptin receptor agonist antibody for leptin deficiency
Altarejos J, Pangilinan J, Podgrabinska S, Akinci B, Foss-Freitas M, Neidert A, Ray Y, Zheng W, Kim S, Kamat V, Huang M, Min S, Mastaitis J, Dominguez-Gutierrez G, Kim J, Stevis P, Huang T, Zambrowicz B, Olson W, Godin S, Bradley E, Gewitz A, Baker M, Hench R, Davenport M, Chenevert T, DiPaola F, Yancopoulos G, Murphy A, Herman G, Musser B, Dansky H, Harp J, Gromada J, Sleeman M, Oral E, Olenchock B. Preclinical, randomized phase 1, and compassionate use evaluation of REGN4461, a leptin receptor agonist antibody for leptin deficiency. Science Translational Medicine 2023, 15: eadd4897. PMID: 37992152, DOI: 10.1126/scitranslmed.add4897.Peer-Reviewed Original ResearchConceptsLeptin concentrationsBody weightHepatic steatosisAdipose-derived hormone leptinClass 3 obesityCompassionate use treatmentHigher baseline leptinLeptin knockout miceAcceptable safety profileLower leptin concentrationsPresence of leptinHuman monoclonal antibodyLeptin receptor signalingTreatment of individualsPhase 1Baseline leptinLepr signalingLeptin deficiencyMetabolic sequelaeLiver diseaseClinical benefitSafety profileInsulin resistanceBlood glucoseInsulin sensitivity
2008
Hypothalamic Fatty Acid Metabolism Mediates the Orexigenic Action of Ghrelin
López M, Lage R, Saha AK, Pérez-Tilve D, Vázquez MJ, Varela L, Sangiao-Alvarellos S, Tovar S, Raghay K, Rodríguez-Cuenca S, Deoliveira RM, Castañeda T, Datta R, Dong JZ, Culler M, Sleeman MW, Álvarez C, Gallego R, Lelliott CJ, Carling D, Tschöp MH, Diéguez C, Vidal-Puig A. Hypothalamic Fatty Acid Metabolism Mediates the Orexigenic Action of Ghrelin. Cell Metabolism 2008, 7: 389-399. PMID: 18460330, DOI: 10.1016/j.cmet.2008.03.006.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein Kinase KinasesAnimalsBlotting, WesternCarnitine O-PalmitoyltransferaseFas ReceptorFastingFatty Acid SynthasesFatty AcidsFeeding BehaviorGhrelinHypothalamusIn Situ HybridizationLeptinMaleMalonyl Coenzyme AMiceMice, Inbred C57BLMice, KnockoutMice, ObesePhosphorylationProtein KinasesRatsRats, Sprague-DawleyConceptsHypothalamic fatty acid metabolismFatty acid metabolismFatty acid synthaseAcid metabolismCarnitine palmitoyltransferase 1 activityFatty acid biosynthesisRegion-specific mannerGhrelin's effectsOrexigenic responseHypothalamic levelOrexigenic actionVentromedial nucleusFood intakeCurrent evidenceFAS expressionGhrelinAcid biosynthesisRelevant regulatory systemGenetic approachesProtein kinaseAMPK activityAcid synthaseSpecific inhibitionRegulatory systemPhysiological mechanisms