2024
O-GlcNAc modification in endothelial cells modulates adiposity via fat absorption from the intestine in mice
Ohgaku S, Ida S, Ohashi N, Morino K, Ishikado A, Yanagimachi T, Murata K, Sato D, Ugi S, Nasiri A, Shulman G, Maegawa H, Kume S, Fujita Y. O-GlcNAc modification in endothelial cells modulates adiposity via fat absorption from the intestine in mice. Heliyon 2024, 10: e34490. PMID: 39130439, PMCID: PMC11315187, DOI: 10.1016/j.heliyon.2024.e34490.Peer-Reviewed Original ResearchEndothelial cellsHigh-fat dietControl miceLipid absorptionExpression of VEGFR3Body weightNitric oxide donorReduced body weightKnockout miceTherapeutic strategiesOxide donorDecreased expressionIntercellular junctionsMiceHigh-fatNutrient-sensing mechanismsFat absorptionO-GlcNAcylationGlucose metabolismVE-cadherinMorphological alterationsMetabolic regulatory mechanismsJunction morphologyLipid metabolismO-GlcNAc transferase
2023
O-linked N-acetylglucosamine modification is essential for physiological adipose expansion induced by high-fat feeding
Nakamoto A, Ohashi N, Sugawara L, Morino K, Ida S, Perry R, Sakuma I, Yanagimachi T, Fujita Y, Ugi S, Kume S, Shulman G, Maegawa H. O-linked N-acetylglucosamine modification is essential for physiological adipose expansion induced by high-fat feeding. AJP Endocrinology And Metabolism 2023, 325: e46-e61. PMID: 37224467, PMCID: PMC10292976, DOI: 10.1152/ajpendo.00263.2022.Peer-Reviewed Original ResearchConceptsFKO miceAdipose tissueBody weight gainPrimary cultured adipocytesAdipose expansionFree fatty acidsInflammatory genesWeight gainFree fatty acid effluxCultured adipocytesDiet-induced obesityHigh-fat dietHigh-fat feedingLess body weightDe novo lipogenesisAdipose tissue physiologyDe novo lipogenesis genesFatty acid effluxWeeks of ageAdipose inflammationGlucose intoleranceRAW 264.7 macrophagesControl miceFatty acidsSevere fibrosis
2021
Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol – PKCε – insulin receptorT1160 phosphorylation
Lyu K, Zhang D, Song J, Li X, Perry RJ, Samuel VT, Shulman GI. Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol – PKCε – insulin receptorT1160 phosphorylation. JCI Insight 2021, 6: e139946. PMID: 33411692, PMCID: PMC7934919, DOI: 10.1172/jci.insight.139946.Peer-Reviewed Original ResearchConceptsInsulin resistanceInsulin actionAdipose tissue insulin resistanceTissue insulin resistanceWT control miceHyperinsulinemic-euglycemic clampShort-term HFDTissue insulin actionAdipose tissue insulin actionDiet-fed ratsPotential therapeutic targetHFD feedingControl miceInsulin sensitivityTherapeutic targetLipolysis suppressionImpairs insulinHFDPKCε activationGlucose uptakeΕ activationMiceDiacylglycerol accumulationRecent evidenceProtein kinase C
2020
Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice
Abulizi A, Vatner DF, Ye Z, Wang Y, Camporez JP, Zhang D, Kahn M, Lyu K, Sirwi A, Cline GW, Hussain MM, Aspichueta P, Samuel VT, Shulman GI. Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice. Journal Of Lipid Research 2020, 61: 1565-1576. PMID: 32907986, PMCID: PMC7707176, DOI: 10.1194/jlr.ra119000586.Peer-Reviewed Original ResearchConceptsHepatic insulin resistanceInsulin resistanceHepatic insulin sensitivityHepatic steatosisLipid-induced hepatic insulin resistancePKCε activationInsulin sensitivityKnockout miceNormal hepatic insulin sensitivityWild-type control miceHepatic ceramide contentHyperinsulinemic-euglycemic clampComprehensive metabolic phenotypingLipid dropletsHepatic DAG contentDAG contentGlucose intoleranceControl miceMTTP activityHepatic insulinAnimal modelsSteatosisAKT Ser/ThrMiceMetabolic phenotyping
2000
Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle
Kim J, Michael M, Previs S, Peroni O, Mauvais-Jarvis F, Neschen S, Kahn B, Kahn C, Shulman G. Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle. Journal Of Clinical Investigation 2000, 105: 1791-1797. PMID: 10862794, PMCID: PMC378504, DOI: 10.1172/jci8305.Peer-Reviewed Original ResearchConceptsInsulin resistanceSelective insulin resistanceMIRKO miceType 2 diabetesHyperinsulinemic-euglycemic conditionsInsulin-stimulated muscle glucose transportMuscle glucose transportMuscle-specific inactivationPrediabetic syndromeGlucose transportControl miceFat massInsulin receptor geneInsulin actionMiceRedistribution of substratesSkeletal muscleImportant associationPotential mechanismsReceptor geneObesityGlycogen synthesisTissueMuscleAdiposity