2024
1886-LB: Safety, PK, and Preliminary Efficacy of the Liver-Targeted Mitochondrial Protonophore TLC-6740—A Phase 1 Study
GANE E, HUSS R, SUR J, MURAKAMI E, WENG S, KIRBY B, SHAH A, SHULMAN G, SUBRAMANIAN M, VIJAYAKUMAR A, MYERS R. 1886-LB: Safety, PK, and Preliminary Efficacy of the Liver-Targeted Mitochondrial Protonophore TLC-6740—A Phase 1 Study. Diabetes 2024, 73 DOI: 10.2337/db24-1886-lb.Peer-Reviewed Original ResearchTreatment of obesityAdverse eventsSteady-state half-lifeEvaluate food effectsPhase 1 studyDose-dependent improvementDose-dependent reductionProportion of subjectsUnrelated to treatmentDose-dependent mannerMAD cohortsLab abnormalitiesSerum totalLDL-CFood effectHealthy subjectsClinical useWeight lossImpact of foodBody weightPreliminary efficacyObesityHalf-lifeTreatmentMitochondrial uncoupling
2008
N-acylphosphatidylethanolamine, a Gut- Derived Circulating Factor Induced by Fat Ingestion, Inhibits Food Intake
Gillum MP, Zhang D, Zhang XM, Erion DM, Jamison RA, Choi C, Dong J, Shanabrough M, Duenas HR, Frederick DW, Hsiao JJ, Horvath TL, Lo CM, Tso P, Cline GW, Shulman GI. N-acylphosphatidylethanolamine, a Gut- Derived Circulating Factor Induced by Fat Ingestion, Inhibits Food Intake. Cell 2008, 135: 813-824. PMID: 19041747, PMCID: PMC2643061, DOI: 10.1016/j.cell.2008.10.043.Peer-Reviewed Original ResearchConceptsFood intakeInhibits food intakeTreatment of obesityNovel therapeutic targetCentral nervous systemUnknown physiological significanceFat ingestionCirculating factorsN-acylphosphatidylethanolaminePlasma lipidsIntracerebroventricular infusionPhysiologic dosesSystemic administrationTherapeutic targetBody weightNervous systemIngested fatSmall intestineIntakeTaste aversionInfusionPhysiological significanceNanomolar amountsObesityHypothalamus