2023
Innate 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
2021
IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2
Goldberg EL, Shchukina I, Youm YH, Ryu S, Tsusaka T, Young KC, Camell CD, Dlugos T, Artyomov MN, Dixit VD. IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2. Cell Metabolism 2021, 33: 2277-2287.e5. PMID: 34473956, PMCID: PMC9067336, DOI: 10.1016/j.cmet.2021.08.004.Peer-Reviewed Original ResearchConceptsOld miceType 2 innate lymphoid cellsInnate lymphoid cellsTissue-resident cellsCore body temperatureAdoptive transferIL-33ILC2 numbersTissue inflammationAged miceImmunometabolic responsesMetabolic impairmentLymphoid cellsDietary restrictionImmune systemILC2Functional defectsMiceBody temperatureFailureCellsInflammationTranscriptomic analysisInfectionStress responseKetogenic diet restrains aging-induced exacerbation of coronavirus infection in mice
Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. ELife 2021, 10: e66522. PMID: 34151773, PMCID: PMC8245129, DOI: 10.7554/elife.66522.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietCoronavirus infectionAged miceT cellsHigher systemic inflammationInfected aged miceCOVID-19 severityCOVID-19 infectionActivation of ketogenesisMouse hepatitis virus strain A59Systemic inflammationInflammatory damageInfluenza infectionClinical hallmarkNLRP3 inflammasomeImmune surveillanceAdipose tissuePotential treatmentInfectionMiceStrongest predictorLungMortalityAge
2018
GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia
Li NX, Brown S, Kowalski T, Wu M, Yang L, Dai G, Petrov A, Ding Y, Dlugos T, Wood H, Wang L, Erion M, Sherwin R, Kelley DE. GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia. Diabetes 2018, 67: db180031. PMID: 29669745, PMCID: PMC6014553, DOI: 10.2337/db18-0031.Peer-Reviewed Original ResearchConceptsSTZ-diabetic ratsGlucagon secretionGPR119 agonistsGlucagon counterregulatory responseGPR119 knockout miceIntensive insulin therapyInsulin-Induced HypoglycemiaHypoglycemic clamp studiesG protein-coupled receptorsGPR119 agonismIncretin secretionInsulin therapyCounterregulatory responsesDiabetic rodentsHypoglycemic clampIatrogenic hypoglycemiaDiabetic ratsGlucagon releaseKO miceRecurrent boutsAgonist pretreatmentClamp studiesIsolated isletsStimulatory actionCultured islets