2023
Calponin 2 regulates ketogenesis to mitigate acute kidney injury
Gui Y, Palanza Z, Gupta P, Li H, Pan Y, Wang Y, Hargis G, Kreutzer D, Wang Y, Bastacky S, Liu Y, Liu S, Zhou D. Calponin 2 regulates ketogenesis to mitigate acute kidney injury. JCI Insight 2023, 8: e170521. PMID: 37751293, PMCID: PMC10721266, DOI: 10.1172/jci.insight.170521.Peer-Reviewed Original ResearchConceptsAcute kidney injuryEstrogen receptor 2Fatty acid oxidationKidney injuryKidney fibrosisCalponin 2Ketone body β-hydroxybutyrateTubular cell deathBody β-hydroxybutyrateSirtuin 5Endogenous ketogenesisKidney functionReceptor 2Protein posttranslational modificationsRate-limiting enzymeFAO pathwayMitochondrial sirtuin 5Animal kidneysΒ-hydroxybutyrateOrgan performanceCell proliferationSynthase 2FibrosisPosttranslational modificationsInjuryInnate immune cell-intrinsic ketogenesis is dispensable for organismal metabolism and age-related inflammation
Goldberg E, Letian A, Dlugos T, Leveau C, Dixit V. Innate immune cell-intrinsic ketogenesis is dispensable for organismal metabolism and age-related inflammation. Journal Of Biological Chemistry 2023, 299: 103005. PMID: 36775129, PMCID: PMC10025153, DOI: 10.1016/j.jbc.2023.103005.Peer-Reviewed Original ResearchConceptsAge-related inflammationKetone bodiesOrganismal metabolismMyeloid cellsChronic low-grade inflammationKetogenic diet feedingLow-grade inflammationHigh-fat dietAbundant ketone bodyGlucose toleranceNLRP3 inflammasomeDiet feedingGlucose homeostasisMouse modelBody weightInflammationMetabolic checkpointOnly organConditional ablationTerminal enzymeΒ-hydroxybutyrateFunctional targetingMethylglutaryl-CoA lyaseKetogenesisModest effect
2022
SGLT2i Improves Glycemic Control in Patients With Congenital Severe Insulin Resistance.
Galderisi A, Tamborlane W, Taylor SI, Attia N, Moretti C, Barbetti F. SGLT2i Improves Glycemic Control in Patients With Congenital Severe Insulin Resistance. 2022, 150 PMID: 35652305, DOI: 10.1542/peds.2021-055671.Peer-Reviewed Original ResearchConceptsRabson-Mendenhall syndromeGlycemic controlHemoglobin A1cRenal calcium excretionInsulin-resistant diabetesSevere insulin resistanceCalcium excretionUrinary calciumAntidiabetic treatmentDay doseDose escalationSecond patientFirst patientInsulin levelsInsulin resistanceUrinary excretionSerum glucosePatientsEmpagliflozinMild increaseDapagliflozinΒ-hydroxybutyrateTarget rangeA1CExcretion
2020
Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue
Goldberg EL, Shchukina I, Asher JL, Sidorov S, Artyomov MN, Dixit VD. Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue. Nature Metabolism 2020, 2: 50-61. PMID: 32694683, PMCID: PMC10150608, DOI: 10.1038/s42255-019-0160-6.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietT cellsAdipose tissue inflammationResident immune cellsVisceral adipose tissueHigher fat compositionReduced adipose tissue inflammationCause obesityMetabolic healthTissue inflammationImmune cellsImmunometabolic responsesProlonged exerciseGlucose homeostasisAdipose tissueInflammationKetone bodiesSingle-cell RNA sequencingLow carbohydrateEnergy homeostasisΒ-hydroxybutyrateFat compositionRNA sequencingCells
2018
Influence of Exogenous β-Hydroxybutyrate on Walking Economy and Rating of Perceived Exertion
James S, Greer B. Influence of Exogenous β-Hydroxybutyrate on Walking Economy and Rating of Perceived Exertion. Journal Of Dietary Supplements 2018, 16: 463-469. PMID: 29953297, DOI: 10.1080/19390211.2018.1471562.Peer-Reviewed Original ResearchConceptsRespiratory exchange ratioEnergy expenditureΒ-hydroxybutyrateExogenous β-hydroxybutyratePlacebo 30 minutesBruce treadmill protocolElevated postexerciseBlood BHB concentrationsBlood glucoseErgogenic benefitsBlood ketonesTreadmill protocolHealthy individualsCrossover designBaseline levelsTrial differencesExchange ratioCON conditionTime pointsPerceived ExertionBHB concentrationsGlucose concentrationOxygen consumptionExertionSupplementationβ-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway
Chen Y, Ouyang X, Hoque R, Garcia-Martinez I, Yousaf MN, Tonack S, Offermanns S, Dubuquoy L, Louvet A, Mathurin P, Massey V, Schnabl B, Bataller R, Mehal WZ. β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway. Journal Of Hepatology 2018, 69: 687-696. PMID: 29705237, PMCID: PMC6098974, DOI: 10.1016/j.jhep.2018.04.004.Peer-Reviewed Original ResearchConceptsAlcohol-induced liver injuryAlcoholic hepatitisAlanine aminotransferase levelsLiver injuryNeutrophil influxAminotransferase levelsΒ-hydroxybutyrateDevelopment of AHPlasma alanine aminotransferase levelsGreater neutrophil influxExcess alcohol intakeAlcoholic liver diseaseLife-threatening conditionExcess alcohol consumptionDependent pathwayHigher plasma alanine aminotransferase levelsIntrahepatic macrophagesLiver inflammationLiver diseaseAlcohol intakeHepatoprotective roleReduced steatosisM2 phenotypeTherapeutic effectHepatitis
2017
Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study
Patel NS, Van Name MA, Cengiz E, Carria LR, Weinzimer SA, Tamborlane WV, Sherr JL. Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study. Diabetes Technology & Therapeutics 2017, 19: 618-622. PMID: 29068709, PMCID: PMC5689123, DOI: 10.1089/dia.2017.0267.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter 2 inhibitorsPlasma glucoseType 1 diabetesDiabetic ketoacidosisFree fatty acidsCANA treatmentBasal insulinGlucagon levelsMetabolic decompensationPlasma insulinInfusion site problemsCotransporter 2 inhibitorsBaseline plasma glucoseFailure of patientsBasal insulin infusionAdjunctive treatmentRate of ketogenesisSGLT2 inhibitorsT1D patientsT1D participantsInsulin infusionMagnitude of increasePG levelsSuspension studiesΒ-hydroxybutyrateβ-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares
Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.Peer-Reviewed Original ResearchConceptsKetogenic dietGouty flaresΒ-hydroxybutyrateMajor risk factorAnti-inflammatory moleculesNLRP3-dependent mannerAlternate metabolic fuelsGout flaresJoint destructionIL-1βIntense painInterleukin-1βNLRP3 inflammasomeRisk factorsInflammatory neutrophilsBacterial infectionsNeutrophilsNLRP3Immune defenseGoutMetabolic fuelsBHBS100A9 fibrilsDietPain
2015
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease
Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D'Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nature Medicine 2015, 21: 263-269. PMID: 25686106, PMCID: PMC4352123, DOI: 10.1038/nm.3804.Peer-Reviewed Original Research
2000
Human Brain β-Hydroxybutyrate and Lactate Increase in Fasting-Induced Ketosis
Pan J, Rothman D, Behar K, Stein D, Hetherington H. Human Brain β-Hydroxybutyrate and Lactate Increase in Fasting-Induced Ketosis. Cerebrovascular And Brain Metabolism Reviews 2000, 20: 1502-1507. PMID: 11043913, DOI: 10.1097/00004647-200010000-00012.Peer-Reviewed Original ResearchConceptsBHB levelsPlasma BHB levelsField magnetic resonance spectroscopyHigh-field magnetic resonance spectroscopyBrain lactateKetogenic dietCalcarine fissureNonfasted stateOccipital lobeHealthy adultsLactate increaseThird dayΒ-hydroxybutyrateKetosisBHB concentrationsBrainBHBGlucose phosphorylationLactate oxidationMagnetic resonance spectroscopy
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