2020
Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice
Tan Y, Hang F, Liu ZW, Stoiljkovic M, Wu M, Tu Y, Han W, Lee AM, Kelley C, Hajos M, Lu L, de Lecea L, de Araujo I, Picciotto M, Horvath TL, Gao XB. Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice. Journal Of Clinical Investigation 2020, 130: 4985-4998. PMID: 32516139, PMCID: PMC7456212, DOI: 10.1172/jci130889.Peer-Reviewed Original ResearchConceptsHcrt cellsObese miceDiet-induced obese miceObese male miceExcessive energy intakeNeuropeptide hypocretin/orexinHypocretin/orexinHcrt neuronsMale miceHcrt systemClinical studiesCommon causeSynaptic transmissionObese animalsEnergy intakeAcute stressCognitive functionSalient stimuliAlters responsesExact mechanismMiceHomeostatic regulationNeuronal networksBehavioral changesNeurons
2018
Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity
Timper K, Paeger L, Sánchez-Lasheras C, Varela L, Jais A, Nolte H, Vogt MC, Hausen AC, Heilinger C, Evers N, Pospisilik JA, Penninger JM, Taylor EB, Horvath TL, Kloppenburg P, Brüning JC. Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity. Cell Reports 2018, 25: 383-397.e10. PMID: 30304679, PMCID: PMC6349418, DOI: 10.1016/j.celrep.2018.09.034.Peer-Reviewed Original ResearchConceptsPOMC neuronsApoptosis-inducing factorImproved glucose metabolismFatty acid utilizationDecrease firingPomc-CreFatty acid metabolismHFD feedingReactive oxygen species formationSystemic glucoseHypothalamic proopiomelanocortinLean miceMitochondrial respirationObese miceObese conditionsInsulin sensitivityGlucose homeostasisGlucose metabolismMild impairmentOxygen species formationFiring propertiesNeuronsOxidative phosphorylationMicePartial impairmentMyeloid sirtuin1 deficiency aggravates hippocampal inflammation in mice fed high-fat diets
Kim KE, Jeong EA, Lee JY, Yi CO, Park KA, Jin Z, Lee JE, Horvath TL, Roh GS. Myeloid sirtuin1 deficiency aggravates hippocampal inflammation in mice fed high-fat diets. Biochemical And Biophysical Research Communications 2018, 499: 1025-1031. PMID: 29634925, DOI: 10.1016/j.bbrc.2018.04.044.Peer-Reviewed Original ResearchConceptsSirt1 KO miceHigh-fat dietInsulin resistanceKO miceLipocalin-2Inflammation-induced insulin resistanceObesity-associated insulin resistanceAnti-inflammatory effectsPrecursor protein levelsWild-type miceHippocampal inflammationWT miceMacrophage infiltrationObese miceLCN2 expressionSIRT1 knockoutType miceHFDAdipose tissueMiceProtein levelsNeuroinflammationSIRT1DietDeficiency
2012
A marriage made to last in drug design
Dietrich MO, Horvath TL. A marriage made to last in drug design. Nature Medicine 2012, 18: 1737-1738. PMID: 23223057, DOI: 10.1038/nm.3018.Peer-Reviewed Original Research
2003
Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice
Horvath TL, Diano S, Miyamoto S, Barry S, Gatti S, Alberati D, Livak F, Lombardi A, Moreno M, Goglia F, Mor G, Hamilton J, Kachinskas D, Horwitz B, Warden CH. Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice. International Journal Of Obesity 2003, 27: 433-442. PMID: 12664076, DOI: 10.1038/sj.ijo.0802257.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBasal MetabolismBlotting, NorthernBlotting, WesternBody TemperatureCarrier ProteinsCholesterol, LDLEnergy IntakeGene Expression RegulationHeart RateInflammationIon ChannelsMaleMembrane Transport ProteinsMiceMice, Inbred C57BLMice, TransgenicMitochondriaMitochondrial ProteinsObesityProteinsUncoupling Protein 2Uncoupling Protein 3ConceptsTransgenic miceFat massLow-density lipoprotein cholesterol levelsHeterozygous miceAgouti obese miceHypothalamic neuropeptide levelsSpontaneous physical activityLipoprotein cholesterol levelsNontransgenic littermate controlsFat pad weightEndotoxin-induced feverWild-type littermatesHuman UCP2Significant differencesMechanism of actionLDL cholesterolControl miceFemale transgenicsNontransgenic littermatesObese miceEndotoxin injectionCholesterol levelsPad weightNeuropeptide levelsFood intake