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 impairmentBrown adipose tissue derived ANGPTL4 controls glucose and lipid metabolism and regulates thermogenesis
Singh AK, Aryal B, Chaube B, Rotllan N, Varela L, Horvath TL, Suárez Y, Fernández-Hernando C. Brown adipose tissue derived ANGPTL4 controls glucose and lipid metabolism and regulates thermogenesis. Molecular Metabolism 2018, 11: 59-69. PMID: 29627378, PMCID: PMC6001401, DOI: 10.1016/j.molmet.2018.03.011.Peer-Reviewed Original ResearchConceptsBrown adipose tissueAdipose tissueAbsence of ANGPTL4Lipoprotein metabolismLPL activityShort-term HFD feedingTriglyceride-rich lipoprotein catabolismLipoprotein lipaseRole of ANGPTL4Novel mouse modelAcute cold exposureGlucose toleranceHFD feedingFatty acidsLipoprotein catabolismWhole body lipidGlucose homeostasisMouse modelGlucose metabolismTAG clearanceBAT resultsLipid metabolismANGPTL4Cold exposureFA oxidation
2014
Neonatal Insulin Action Impairs Hypothalamic Neurocircuit Formation in Response to Maternal High-Fat Feeding
Vogt MC, Paeger L, Hess S, Steculorum SM, Awazawa M, Hampel B, Neupert S, Nicholls HT, Mauer J, Hausen AC, Predel R, Kloppenburg P, Horvath TL, Brüning JC. Neonatal Insulin Action Impairs Hypothalamic Neurocircuit Formation in Response to Maternal High-Fat Feeding. Cell 2014, 156: 495-509. PMID: 24462248, PMCID: PMC4101521, DOI: 10.1016/j.cell.2014.01.008.Peer-Reviewed Original ResearchConceptsPOMC neuronsMaternal high-fat diet (HFD) feedingOrexigenic agouti-related peptide (AgRP) neuronsHealth outcomesMaternal high-fat feedingHigh-fat diet feedingImpaired glucose-stimulated insulin secretionMaternal HFD feedingGlucose-stimulated insulin secretionImpaired glucose homeostasisOffspring health outcomesHigh-fat feedingPOMC projectionsParasympathetic innervationHFD feedingMaternal overnutritionPeptide neuronsAbnormal insulinAnorexigenic proopiomelanocortinParaventricular nucleusDiet feedingInsulin secretionMelanocortin circuitryNeuropeptide expressionLong-term effects
2011
Obesity is associated with hypothalamic injury in rodents and humans
Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW. Obesity is associated with hypothalamic injury in rodents and humans. Journal Of Clinical Investigation 2011, 122: 153-162. PMID: 22201683, PMCID: PMC3248304, DOI: 10.1172/jci59660.Peer-Reviewed Original ResearchConceptsHigh-fat dietHFD feedingMediobasal hypothalamusPeripheral tissuesRodent modelsBody weight controlHypothalamic arcuate nucleusSubstantial weight gainConsequences of obesityNeuron injuryHypothalamic injuryNeuronal injuryNeuroprotective mechanismsReactive gliosisObese humansHypothalamic areaArcuate nucleusInflammatory signalingBrain areasWeight controlObesityGliosisEnergy homeostasisWeight gainInflammation