2023
Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition
Sakuma I, Gaspar R, Luukkonen P, Kahn M, Zhang D, Zhang X, Murray S, Golla J, Vatner D, Samuel V, Petersen K, Shulman G. Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2312666120. PMID: 38127985, PMCID: PMC10756285, DOI: 10.1073/pnas.2312666120.Peer-Reviewed Original Research
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
Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice
Li X, Zhang D, Vatner DF, Goedeke L, Hirabara SM, Zhang Y, Perry RJ, Shulman GI. Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 32584-32593. PMID: 33293421, PMCID: PMC7768680, DOI: 10.1073/pnas.1922169117.Peer-Reviewed Original ResearchConceptsEpididymal white adipose tissueInsulin resistanceAdiponectin treatmentAdipose tissueHigh-fat diet-induced insulin resistanceType 2 diabetes mellitusWhole-body insulin resistanceDiet-induced insulin resistanceSkeletal muscleEctopic lipid storageReverses insulin resistanceInsulin-mediated suppressionMuscle fatty acid oxidationEndogenous glucose productionMuscle insulin resistanceWhite adipose tissueLipoprotein lipase activityMuscle fat oxidationPKCε translocationInsulin-stimulated glucose uptakeFatty acid oxidationTAG uptakeDiabetes mellitusMuscle sensitivityAkt serine phosphorylationMitochondrial Dysfunction, Insulin Resistance, and Potential Genetic Implications
Sangwung P, Petersen KF, Shulman GI, Knowles JW. Mitochondrial Dysfunction, Insulin Resistance, and Potential Genetic Implications. Endocrinology 2020, 161: bqaa017. PMID: 32060542, PMCID: PMC7341556, DOI: 10.1210/endocr/bqaa017.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, WhiteDiabetes Mellitus, Type 2HumansInsulin ResistanceLipid MetabolismLiverMitochondriaMuscle, SkeletalPrediabetic StateConceptsInsulin resistanceWhole-body insulin resistanceMitochondrial functionEctopic lipid depositionBody insulin resistanceType 2 diabetesWhite adipose tissuePrediabetic individualsVivo metabolic studiesInsulin-responsive tissuesLipid depositionAdipose tissueType 2Skeletal muscleMitochondrial dysfunctionPotential mechanismsMetabolic studiesHuman genetic studiesTissueEnvironmental determinantsMitochondrial malfunctionCellular energy balanceRecent insightsCritical roleDiabetes
2019
Anti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance
Camporez JP, Lyu K, Goldberg EL, Zhang D, Cline GW, Jurczak MJ, Dixit VD, Petersen KF, Shulman GI. Anti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance. The Journal Of Physiology 2019, 597: 3885-3903. PMID: 31206703, PMCID: PMC6876753, DOI: 10.1113/jp277270.Peer-Reviewed Original ResearchConceptsObesity-induced insulin resistanceHigh-fat dietEctopic lipid contentWhite adipose tissue lipolysisInsulin resistanceAdipose tissue lipolysisMale miceInsulin sensitivityFemale miceInsulin-stimulated suppressionWAT inflammationTissue lipolysisRodent studiesTumor necrosis factor αWhole-body insulin sensitivityLipid-induced insulin resistanceMetabolic homeostasisAge-matched menInterleukin-6 concentrationsSkeletal muscleAnti-inflammatory effectsType 2 diabetesInsulin-mediated suppressionSexual dimorphic responseNecrosis factor α