2024
Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring
Sun J, Esplugues E, Bort A, Cardelo M, Ruz-Maldonado I, Fernández-Tussy P, Wong C, Wang H, Ojima I, Kaczocha M, Perry R, Suárez Y, Fernández-Hernando C. Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring. Nature Metabolism 2024, 6: 741-763. PMID: 38664583, DOI: 10.1038/s42255-024-01019-6.Peer-Reviewed Original ResearchConceptsFatty acid binding protein 5Tumor-associated macrophagesHepatocellular carcinomaImmunosuppressive phenotype of tumor-associated macrophagesIncreased CD8+ T cell activationCD8+ T cell activationPhenotype of tumor-associated macrophagesPro-inflammatory tumor microenvironmentCo-stimulatory molecules CD80T cell activationHepatocellular carcinoma burdenTransformation of hepatocytesBinding protein 5Potential therapeutic approachImmunosuppressive phenotypeTumor microenvironmentFerroptosis-induced cell deathMale miceEnhanced ferroptosisTherapeutic approachesPharmacological inhibitionGenetic ablationIncreased expressionSingle-cell atlasAnalysis of transformed cellsA New Mitochondrial Uncoupler Improves Metabolic Homeostasis in Mice.
Ramshankar G, Perry R. A New Mitochondrial Uncoupler Improves Metabolic Homeostasis in Mice. Diabetes 2024, 73: 357-358. PMID: 38377448, DOI: 10.2337/dbi23-0033.Commentaries, Editorials and LettersMetabolic 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
2022
Insulin and cancer: a tangled web
Leitner BP, Siebel S, Akingbesote ND, Zhang X, Perry RJ. Insulin and cancer: a tangled web. Biochemical Journal 2022, 479: 583-607. PMID: 35244142, PMCID: PMC9022985, DOI: 10.1042/bcj20210134.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
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
Hepatic 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