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
2007
Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure
Pfluger PT, Kirchner H, Günnel S, Schrott B, Perez-Tilve D, Fu S, Benoit SC, Horvath T, Joost HG, Wortley KE, Sleeman MW, Tschöp M. Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure. AJP Gastrointestinal And Liver Physiology 2007, 294: g610-g618. PMID: 18048479, DOI: 10.1152/ajpgi.00321.2007.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAnthropometryBlood GlucoseBody CompositionBody TemperatureBody WeightEatingEnergy MetabolismGene DeletionGenotypeGhrelinGlucose Tolerance TestInsulin ResistanceLigandsLipidsMiceMice, KnockoutMotor ActivityReceptors, GhrelinReverse Transcriptase Polymerase Chain ReactionRNA, MessengerConceptsFood intakeSimultaneous deletionStandard dietHigh-fat diet-induced obesityMotor activityWild-type control miceFirst mouse mutantsMetabolic phenotypeDiet-induced obesityEnergy metabolism phenotypesEnergy expenditureGene-deficient miceKnockout mice exhibitSingle gene-deficient miceSame genetic backgroundMost speciesWT miceControl miceStandard chowMolecular controlBody adiposityBiological roleLean massMouse mutantsMeal patterns