2020
GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function
Timper K, del Río-Martín A, Cremer AL, Bremser S, Alber J, Giavalisco P, Varela L, Heilinger C, Nolte H, Trifunovic A, Horvath TL, Kloppenburg P, Backes H, Brüning JC. GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function. Cell Metabolism 2020, 31: 1189-1205.e13. PMID: 32433922, PMCID: PMC7272126, DOI: 10.1016/j.cmet.2020.05.001.Peer-Reviewed Original Research
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 oxidationAbsence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis
Aryal B, Singh AK, Zhang X, Varela L, Rotllan N, Goedeke L, Chaube B, Camporez JP, Vatner DF, Horvath TL, Shulman GI, Suárez Y, Fernández-Hernando C. Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis. JCI Insight 2018, 3: e97918. PMID: 29563332, PMCID: PMC5926923, DOI: 10.1172/jci.insight.97918.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAllelesAngiopoietin-Like Protein 4AnimalsAtherosclerosisBody WeightChemokinesCytokinesDiet, High-FatDiet, WesternFatty AcidsGene Expression ProfilingGene Expression RegulationGene Knockout TechniquesGlucoseInsulinIntegrasesIntercellular Signaling Peptides and ProteinsLipid MetabolismLipoprotein LipaseLipoproteinsLiverMaleMiceMice, Inbred C57BLMice, KnockoutMusclesObesityProprotein Convertase 9TriglyceridesConceptsAngiopoietin-like protein 4High-fat dietEctopic lipid depositionLipid depositionGlucose toleranceLipoprotein lipaseShort-term high-fat dietSevere metabolic abnormalitiesProgression of atherosclerosisMajor risk factorTriacylglycerol-rich lipoproteinsFatty acid uptakeAdipose tissue resultsProatherogenic lipoproteinsCardiometabolic diseasesMetabolic abnormalitiesKO miceRisk factorsWhole body lipidMetabolic disordersGlucose metabolismLPL activityAdipose tissueGenetic ablationRapid clearance
2008
UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschöp MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL, Diano S. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature 2008, 454: 846-851. PMID: 18668043, PMCID: PMC4101536, DOI: 10.1038/nature07181.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsCarnitine O-PalmitoyltransferaseFatty AcidsFeeding BehaviorGene Expression RegulationGhrelinHypothalamusIon ChannelsMembrane Potential, MitochondrialMiceMitochondriaMitochondrial ProteinsNeuronsNeuropeptide YPhosphorylationReactive Oxygen SpeciesSynapsesUncoupling Protein 2ConceptsNPY/AgRP neuronsAgRP neuronsNeuronal activityCo-express neuropeptide YGut-derived hormone ghrelinAgRP neuronal activityArcuate nucleus neuronsFatty acid oxidation pathwayHypothalamic mitochondrial respirationG protein-coupled receptorsGhrelin actionNeuropeptide YNucleus neuronsHormone ghrelinFood intakeGhrelinFree radicalsSynaptic plasticityNeuronal functionIntracellular mechanismsNeuronsMitochondrial mechanismsProtein 2Mitochondrial proliferationRobust changes