2024
The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose
Mashayekhi M, Sheng Q, Bailin S, Massier L, Zhong J, Shi M, Wanjalla C, Wang T, Ikizler T, Niswender K, Gabriel C, Palacios J, Turgeon‐Jones R, Reynolds C, Luther J, Brown N, Das S, Dahlman I, Mosley J, Koethe J, Rydén M, Bachmann K, Shah R. The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose. Obesity 2024, 32: 1526-1540. PMID: 38967296, PMCID: PMC11269023, DOI: 10.1002/oby.24064.Peer-Reviewed Original ResearchVisceral adipose tissueExpression quantitative trait lociSubcutaneous adipose tissueGenetic effect sizesQuantitative trait lociInsulin resistanceAdipocyte transcriptsSat geneAdipose transcriptomeTrait lociTranscriptional architectureTranscriptional landscapeMetabolic bufferRNA sequencingInsulin stimulationAdipose tissueNon-immune cell populationsMetabolic phenotypeWeight loss surgeryNon-immune populationSpectrum of obesityCardiometabolic disease riskMacrophage transcriptionMolecular signaturesType 2 diabetes
2022
Comparative effects of weight loss and incretin‐based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial
Mashayekhi M, Beckman JA, Nian H, Garner EM, Mayfield D, Devin JK, Koethe JR, Brown JD, Cahill KN, Yu C, Silver H, Niswender K, Luther JM, Brown NJ. Comparative effects of weight loss and incretin‐based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial. Diabetes Obesity And Metabolism 2022, 25: 570-580. PMID: 36306151, PMCID: PMC10306232, DOI: 10.1111/dom.14903.Peer-Reviewed Original ResearchConceptsFlow-mediated vasodilationPlasminogen activator inhibitor-1Vascular endothelial functionEndothelial functionInsulin resistanceWeight lossGlucagon-like peptide-1 receptor agonistsBaseline flow-mediated vasodilationDipeptidyl peptidase-4 inhibitor sitagliptinGLP-1R agonist liraglutideWeight loss-independent mechanismsPeptide-1 receptor agonistsBeneficial effectsEndothelial vasodilator functionGreater endothelial dysfunctionIncretin-based therapiesNormal endothelial functionChemoattractant protein-1Chemokine MCP-1Significant weight lossActivator inhibitor-1Effect of treatmentVasodilator functionUrine albuminEndothelial dysfunction
2018
The Vasculature in Prediabetes
Wasserman DH, Wang TJ, Brown NJ. The Vasculature in Prediabetes. Circulation Research 2018, 122: 1135-1150. PMID: 29650631, PMCID: PMC5901903, DOI: 10.1161/circresaha.118.311912.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme InhibitorsAnimalsBlood VesselsCardiovascular DiseasesCombined Modality TherapyDiabetes Mellitus, Type 2Diet, ReducingDisease ProgressionEndothelium, VascularExtracellular MatrixFatty Acids, NonesterifiedFibrinolysisGlucoseHumansHyperglycemiaHypoglycemic AgentsInflammationInsulin ResistanceLife StyleMetabolic SyndromeMiceMicrocirculationMicroRNAsMuscle, SkeletalObesityPrediabetic StateRiskWeight LossConceptsFrequency of prediabetesMainstay of treatmentPrevalence of obesityConcomitant obesityEndothelial dysfunctionExtracellular matrix remodelingDiabetes mellitusEndothelial functionRenal diseaseMetabolic derangementsFibrinolytic dysfunctionEndothelial vasodilatorsInsulin resistanceInsulin sensitivityCardiovascular diseaseDelivery of insulinSlow progressionPrediabetesWeight lossSkeletal muscleMatrix remodelingMellitusObesityDysfunctionDisease
2015
A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics
Baudrand R, Goodarzi MO, Vaidya A, Underwood PC, Williams JS, Jeunemaitre X, Hopkins PN, Brown N, Raby BA, Lasky-Su J, Adler GK, Cui J, Guo X, Taylor KD, Chen YD, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH, Pojoga LH. A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics. Metabolism 2015, 64: 1674-1681. PMID: 26475177, PMCID: PMC4641791, DOI: 10.1016/j.metabol.2015.09.005.Peer-Reviewed Original ResearchConceptsMinor allele carriersAllele carriersMetabolic syndromeInsulin resistanceHigher oddsHigher Framingham risk scoreFramingham risk scoreGene variantsNon-obese subjectsMinor allele carrier statusAllele carrier statusHyperPATH cohortLow HDLMetS diagnosisMetS riskObese subjectsMulticenter studyObesity statusSimilar BMIRisk scoreHispanic cohortClinical implicationsHispanic participantsCohortCarrier status
2014
Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans
Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins And Other Lipid Mediators 2014, 113: 38-44. PMID: 25173047, PMCID: PMC4253976, DOI: 10.1016/j.prostaglandins.2014.08.001.Peer-Reviewed Original ResearchConceptsInsulin sensitivity indexEpoxyeicosatrienoic acidsInsulin sensitivityHigher insulin sensitivity indexPlasma epoxyeicosatrienoic acidsGlucose-stimulated insulin secretionBody mass indexArg/ArgSoluble epoxide hydrolase activitySoluble epoxide hydrolaseMetabolic syndromeMass indexDisposition indexInsulin resistanceHyperglycemic clampInsulin secretionSensitivity indexEpoxide hydrolase activityEPHX2Hydrolase activitySecretionPhenotyping studiesMetabolic phenotyping studiesEpoxide hydrolaseGenetic variants
2011
The renin–angiotensin–aldosterone system and glucose homeostasis
Luther JM, Brown NJ. The renin–angiotensin–aldosterone system and glucose homeostasis. Trends In Pharmacological Sciences 2011, 32: 734-739. PMID: 21880378, PMCID: PMC3223326, DOI: 10.1016/j.tips.2011.07.006.Peer-Reviewed Original ResearchConceptsAldosterone systemΒ-cellsGlucose-stimulated insulin secretionIncidence of diabetesLarge clinical trialsInduces Insulin ResistanceCultured β-cellsPancreatic β-cellsRAAS inhibitionAng IIAngiotensin IIInsulin resistanceHeart diseaseClinical trialsDiabetes progressionMineralocorticoid receptorPharmacological strategiesInsulin secretionGlucose homeostasisPancreatic isletsOxidative stressDiabetesIndependent mechanismsGlucose transportCellular level
2010
Low-salt diet increases insulin resistance in healthy subjects
Garg R, Williams GH, Hurwitz S, Brown NJ, Hopkins PN, Adler GK. Low-salt diet increases insulin resistance in healthy subjects. Metabolism 2010, 60: 965-968. PMID: 21036373, PMCID: PMC3036792, DOI: 10.1016/j.metabol.2010.09.005.Peer-Reviewed Original ResearchConceptsLow-salt dietHomeostasis model assessment indexModel assessment indexBody mass indexInsulin resistanceLS dietUrine aldosteroneMass indexHS dietHealthy subjectsHigher homeostasis model assessment indexUrine norepinephrine excretionPlasma renin activityHigh-salt dietSympathetic nervous systemSerum angiotensin IIPathogenesis of diabetesUrine epinephrineNorepinephrine excretionRenin activitySerum aldosteroneBlood pressureSerum sodiumAngiotensin IIHealthy men
2008
The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension
Laffer CL, Gainer JV, Waterman MR, Capdevila JH, Laniado-Schwartzman M, Nasjletti A, Brown NJ, Elijovich F. The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension. Hypertension 2008, 51: 767-772. PMID: 18227405, PMCID: PMC2365894, DOI: 10.1161/hypertensionaha.107.102921.Peer-Reviewed Original ResearchConceptsBlood pressureC carriersHypertensive subjectsSalt-sensitive hypertensive subjectsHigher diastolic blood pressureT8590C polymorphismSalt-sensitive subjectsDiastolic blood pressureMicroU/mLDahl S ratsSerum insulin concentrationsC allele carriersC allele frequencySalt sensitivityPressure natriuresisEssential hypertensionFractional excretionSerum insulinHip ratioHuman hypertensionInsulin resistanceInsulin sensitivitySodium balanceInsulin concentrationsTT subjects
2004
Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1
Ma LJ, Mao SL, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y, Brown NJ, Swift LL, McGuinness OP, Wasserman DH, Vaughan DE, Fogo AB. Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1. Diabetes 2004, 53: 336-346. PMID: 14747283, DOI: 10.2337/diabetes.53.2.336.Peer-Reviewed Original ResearchMeSH KeywordsAdiponectinAnimalsBlood GlucoseCalorimetry, IndirectCarrier ProteinsDisease Models, AnimalGlucose Clamp TechniqueHyperinsulinismInsulinInsulin ResistanceIntercellular Signaling Peptides and ProteinsIon ChannelsMaleMembrane ProteinsMiceMice, KnockoutMitochondrial ProteinsObesityPlasminogen Activator Inhibitor 1Polymerase Chain ReactionProteinsRNA, MessengerTranscription, GeneticTriglyceridesUncoupling Protein 1Weight GainConceptsPlasminogen activator inhibitor-1Prevention of obesityInsulin resistanceHF dietWT miceActivator inhibitor-1Insulin sensitivityPAI-1Angiotensin type 1 receptor antagonistType 1 receptor antagonistDiet-induced obesity modelEuglycemic hyperinsulinemic clamp studyProtein-3 mRNA expressionInhibitor-1PAI-1-deficient micePeroxisome proliferator-activated receptorDiet-induced obesityPAI-1 levelsPAI-1 deficiencyPAI-1 increaseWhite adipose tissueProliferator-activated receptorInsulin-stimulated glucose uptakeTotal energy expenditureDirect causal role
2002
PAI-1 in human hypertension: relation to hypertensive groups*
Srikumar N, Brown NJ, Hopkins PN, Jeunemaitre X, Hunt SC, Vaughan DE, Williams GH. PAI-1 in human hypertension: relation to hypertensive groups*. American Journal Of Hypertension 2002, 15: 683-690. PMID: 12160190, DOI: 10.1016/s0895-7061(02)02952-7.Peer-Reviewed Original ResearchConceptsPlasma renin activityPAI-1 levelsPlasminogen activator inhibitor type 1Hypertensive subjectsInsulin resistanceLow reninRenin activityHigher PAI-1 levelsDietary salt restrictionLow-salt dietRenin-angiotensin systemActivator inhibitor type 1Inhibitor type 1Aldosterone levelsHypertensive groupSalt restrictionSodium dietSodium restrictionSalt dietHuman hypertensionType 1AldoModulator groupsNonmodulatorsRenin