2024
Deficits in brain glucose transport among younger adults with obesity
Gunawan F, Matson B, Coppoli A, Jiang L, Ding Y, Perry R, Sanchez‐Rangel E, DeAguiar R, Behar K, Rothman D, Mason G, Hwang J. Deficits in brain glucose transport among younger adults with obesity. Obesity 2024, 32: 1329-1338. PMID: 38764181, DOI: 10.1002/oby.24034.Peer-Reviewed Original ResearchBrain glucose transportLean participantsMarkers of insulin resistanceMagnetic resonance spectroscopy scansEffect of obesityAssociated with alterationsLong-term brain functionCerebral glucose metabolic rateGlucose transportGlucose metabolic rateCardiometabolic comorbiditiesBrain energy utilizationPeripheral markersHyperglycemic clampInsulin resistanceObesityBrain glucose uptakeHuman findingsEating behaviorsYounger ageYoung healthy participantsNeurocognitive functionGlucose transport capacityBrain functionNonesterified fatty acidsMetabolic underpinnings of cancer-related fatigue
Zhang X, Perry R. Metabolic underpinnings of cancer-related fatigue. AJP Endocrinology And Metabolism 2024, 326: e290-e307. PMID: 38294698, DOI: 10.1152/ajpendo.00378.2023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCancer-related fatigueMechanisms of cancer-related fatigueInsulin resistanceImpact of obesityCancer-induced painComplication of cancerTarget obesityInduce chronic inflammationObesityNarrative reviewObesity/insulin resistanceTumor growthChronic inflammationDetrimental complicationsCancer patientsMetabolic alterationsClinical researchNeuroendocrinological disturbancesMetabolic underpinningsAnalyzed recent studiesInsulinFatigueBehavioral disruptionPatientsPotential mechanisms
2020
Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis
Perry RJ, Zhang D, Guerra MT, Brill AL, Goedeke L, Nasiri AR, Rabin-Court A, Wang Y, Peng L, Dufour S, Zhang Y, Zhang XM, Butrico GM, Toussaint K, Nozaki Y, Cline GW, Petersen KF, Nathanson MH, Ehrlich BE, Shulman GI. Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis. Nature 2020, 579: 279-283. PMID: 32132708, PMCID: PMC7101062, DOI: 10.1038/s41586-020-2074-6.Peer-Reviewed Original ResearchConceptsHepatic steatosisType 2Nonalcoholic fatty liver diseaseDiet-induced hepatic steatosisFatty liver diseasePlasma glucagon concentrationsHepatic adipose triglyceride lipaseHepatic acetyl-CoA contentHepatic glucose productionRatio of insulinHepatic glucose metabolismInositol triphosphate receptorAdipose triglyceride lipaseMitochondrial oxidationMitochondrial fat oxidationGlucose intoleranceLiver diseaseGlucagon concentrationsInsulin resistancePortal veinAcetyl-CoA contentHepatic lipolysisGlucagon biologyGlucose metabolismKnockout mice
2019
Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation
Rabin-Court A, Rodrigues MR, Zhang XM, Perry RJ. Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation. PLOS ONE 2019, 14: e0218126. PMID: 31188872, PMCID: PMC6561592, DOI: 10.1371/journal.pone.0218126.Peer-Reviewed Original ResearchMeSH KeywordsAlanineBreast NeoplasmsCell Line, TumorCitrate (si)-SynthaseColonic NeoplasmsFemaleGene Expression RegulationGlucoseGlutamic AcidHumansInsulinIsotope LabelingKetone OxidoreductasesLymphoma, B-CellMaleMelanomaMitochondriaObesityOrgan SpecificityOxidation-ReductionPhosphorylationProstatic NeoplasmsReceptor, InsulinSignal TransductionSkin NeoplasmsSmall Cell Lung CarcinomaConceptsCell divisionTumor cell linesCell linesMitochondrial glucose oxidationTumor typesObesity-driven insulin resistanceSubstrate preferenceMolecular mechanismsDose-dependent increaseGlucose oxidationPhysiologic insulinPyruvate dehydrogenase fluxWorse prognosisInsulin resistanceStable isotope methodObesityOxidative responsePhysiologic concentrationsSynthase fluxInsulinMetabolic signaturesTumor cellsTumorsDivisionLines
2017
Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Ferrandino G, Kaspari RR, Spadaro O, Reyna-Neyra A, Perry RJ, Cardone R, Kibbey RG, Shulman GI, Dixit VD, Carrasco N. Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e9172-e9180. PMID: 29073114, PMCID: PMC5664516, DOI: 10.1073/pnas.1707797114.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseDe novo lipogenesisAdipose tissue lipolysisHepatic insulin resistanceThyroid hormonesHypothyroid miceImpaired suppressionInsulin resistanceTissue lipolysisInsulin secretionHigh thyroid-stimulating hormone levelsRegulation of THThyroid-stimulating hormone levelsLipid utilizationFatty liver diseaseSerum glucose levelsEndogenous glucose productionLow thyroid hormoneFatty acidsHepatic lipid utilizationLiver diseaseSevere hypothyroidismHormone levelsProfound suppressionGlucose levels
2016
Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome
Perry RJ, Peng L, Barry NA, Cline GW, Zhang D, Cardone RL, Petersen KF, Kibbey RG, Goodman AL, Shulman GI. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature 2016, 534: 213-217. PMID: 27279214, PMCID: PMC4922538, DOI: 10.1038/nature18309.Peer-Reviewed Original ResearchConceptsGut microbiotaMetabolic syndromeGlucose-stimulated insulin secretionAltered gut microbiotaParasympathetic nervous systemPossible therapeutic targetGhrelin secretionInsulin resistanceInsulin secretionParasympathetic activationTherapeutic targetNervous systemObesityMicrobiota interactionsSyndromeMicrobiotaSecretionActivationSequelaeHyperphagia
2015
Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats
Perry RJ, Zhang D, Zhang XM, Boyer JL, Shulman GI. Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats. Science 2015, 347: 1253-1256. PMID: 25721504, PMCID: PMC4495920, DOI: 10.1126/science.aaa0672.Peer-Reviewed Original ResearchMeSH Keywords2,4-DinitrophenolAnimalsBlood GlucoseDelayed-Action PreparationsDiabetes Mellitus, Type 2Glucose Tolerance TestInsulin ResistanceLipid MetabolismLiver CirrhosisMaleMiceMitochondria, LiverMuscle, SkeletalNon-alcoholic Fatty Liver DiseaseOxidation-ReductionProton IonophoresRandom AllocationRatsRats, ZuckerConceptsNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisInsulin resistanceRat modelControlled-release oral formulationsPlasma transaminase concentrationsFatty liver diseaseType 2 diabetesMitochondrial uncouplingProtein-synthetic functionChronic treatmentLiver diseaseMetabolic syndromeTransaminase concentrationsHepatic steatosisLiver fibrosisEffective therapyPreclinical modelsOral formulationSystemic toxicityClinical useRelated epidemicsBeneficial effectsSynthetic functionMitochondrial protonophoreHepatic Acetyl CoA Links Adipose Tissue Inflammation to Hepatic Insulin Resistance and Type 2 Diabetes
Perry RJ, Camporez JP, Kursawe R, Titchenell PM, Zhang D, Perry CJ, Jurczak MJ, Abudukadier A, Han MS, Zhang XM, Ruan HB, Yang X, Caprio S, Kaech SM, Sul HS, Birnbaum MJ, Davis RJ, Cline GW, Petersen KF, Shulman GI. Hepatic Acetyl CoA Links Adipose Tissue Inflammation to Hepatic Insulin Resistance and Type 2 Diabetes. Cell 2015, 160: 745-758. PMID: 25662011, PMCID: PMC4498261, DOI: 10.1016/j.cell.2015.01.012.Peer-Reviewed Original ResearchConceptsHepatic glucose productionWhite adipose tissueHepatic insulin resistanceInsulin resistanceImpaired insulin-mediated suppressionAdipose tissue inflammationIL-6 neutralizationIL-6 infusionType 2 diabetesInsulin-mediated suppressionSuppression of lipolysisAdipose triglyceride lipaseTissue inflammationAdipose tissueType 2Fed ratsGlucose productionGenetic ablationInsulin's abilityAcetyl CoATriglyceride lipaseInsulin signalingRatsMetabolomics approachInsulin