2025
Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
Rubinelli L, Manzo O, Sungho J, Del Gaudio I, Bareja R, Marino A, Palikhe S, Di Mauro V, Bucci M, Falcone D, Elemento O, Ersoy B, Diano S, Sasset L, Di Lorenzo A. Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases. Nature Communications 2025, 16: 1968. PMID: 40000621, PMCID: PMC11862206, DOI: 10.1038/s41467-025-56869-9.Peer-Reviewed Original ResearchConceptsNogo-BEndothelial dysfunctionHFD miceCardiometabolic diseasesSphingolipid signalingDevelopment of therapeutic strategiesBioactive sphingolipidsCeramide degradationSphingosine-1-phosphateHepatic glucose productionIn vivo evidenceEndothelial cellsEndothelial specific deletionCeramideBiosynthesisHigh-fat dietPathological implicationsSphingolipidsGlucose productionHFDIn vivoMale miceMetabolic dysfunctionTherapeutic strategiesMetabolic disorders
2024
GABAergic disinhibition from the BNST to PNOCARC neurons promotes HFD-induced hyperphagia
Sotelo-Hitschfeld T, Minère M, Klemm P, Borgmann D, Wnuk-Lipinski D, Jais A, Jia X, Corneliussen S, Kloppenburg P, Fenselau H, Brüning J. GABAergic disinhibition from the BNST to PNOCARC neurons promotes HFD-induced hyperphagia. Cell Reports 2024, 43: 114343. PMID: 38865247, DOI: 10.1016/j.celrep.2024.114343.Peer-Reviewed Original ResearchInhibition of POMC neuronsGamma-aminobutyric acidPOMC neuronsArcuate nucleusBed nucleus of the stria terminalisHFD feedingGABAergic disinhibitionAnorexic responseBed nucleusRabies tracingInhibitory inputsStria terminalisObesity developmentNeuronal activityNeuronal circuitsCircuit mappingNeuronsHyperphagiaHFDCaloric contentBNSTTerminalisObesityMicePOMC
2023
1510-P: Lipid-Induced Renal Cortical Insulin Resistance Perturbs Gluconeogenic and Oxidative Metabolism via an sn-1,2-diacylglycerol-PKCe-Insulin Receptor Kinase Axis In Vivo
HUBBARD B, GASPAR R, ZHANG D, KAHN M, NASIRI A, SHULMAN G. 1510-P: Lipid-Induced Renal Cortical Insulin Resistance Perturbs Gluconeogenic and Oxidative Metabolism via an sn-1,2-diacylglycerol-PKCe-Insulin Receptor Kinase Axis In Vivo. Diabetes 2023, 72 DOI: 10.2337/db23-1510-p.Peer-Reviewed Original ResearchInsulin receptor kinasePyruvate carboxylaseHyperinsulinemic-euglycemic clampMitochondrial pyruvate oxidationInsulin resistanceOxidative metabolismMitochondrial pyruvate carboxylaseReceptor kinaseInhibitory phosphorylationAktS473 phosphorylationKinase axisChow fed miceImpairs insulinPyruvate oxidationKnockin micePhosphorylationKey targetFortress BiotechFed micePKCεDiacylglycerolRenal cortexHFDMetabolismBasal conditions
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
High fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow
Bracko O, Vinarcsik L, Cruz Hernández J, Ruiz-Uribe N, Haft-Javaherian M, Falkenhain K, Ramanauskaite E, Ali M, Mohapatra A, Swallow M, Njiru B, Muse V, Michelucci P, Nishimura N, Schaffer C. High fat diet worsens Alzheimer’s disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow. Scientific Reports 2020, 10: 9884. PMID: 32555372, PMCID: PMC7303150, DOI: 10.1038/s41598-020-65908-y.Peer-Reviewed Original ResearchConceptsAPP/PS1 miceAlzheimer's diseaseAPP/PS1 genotypeMouse model of ADAmyloid-beta monomersAD-related pathologyModel of ADHigh-fat dietNeutrophil adhesionAPP/PS1Cerebral blood flowBlocking neutrophil adhesionCapillary stallingIncreased brain inflammationSeverity of Alzheimer's diseaseShort-term memory functionPoorer memory performanceImpaired social interactionSynergistic impairmentFat dietCerebral blood flow deficitsHFDGenotypesSensory-motor functionMemory performance
2018
Effects of myeloid sirtuin 1 deficiency on hypothalamic neurogranin in mice fed a high-fat diet
Kim KE, Jeong EA, Shin HJ, Lee JY, Choi EB, An HS, Park KA, Jin Z, Lee DK, Horvath TL, Roh GS. Effects of myeloid sirtuin 1 deficiency on hypothalamic neurogranin in mice fed a high-fat diet. Biochemical And Biophysical Research Communications 2018, 508: 123-129. PMID: 30471862, DOI: 10.1016/j.bbrc.2018.11.126.Peer-Reviewed Original ResearchConceptsHigh-fat dietHypothalamic inflammationSIRT1 deletionWT miceInsulin resistanceKO miceFood intakeNeurogranin expressionParvalbumin protein levelsSIRT1 knockout miceAnorexigenic proopiomelanocortinArcuate nucleusVentromedial hypothalamusHigher food intakeHFDKnockout miceLow expressionMiceWeight gainInflammationProtein levelsNeurograninHypothalamusIntakeDietMyeloid sirtuin1 deficiency aggravates hippocampal inflammation in mice fed high-fat diets
Kim KE, Jeong EA, Lee JY, Yi CO, Park KA, Jin Z, Lee JE, Horvath TL, Roh GS. Myeloid sirtuin1 deficiency aggravates hippocampal inflammation in mice fed high-fat diets. Biochemical And Biophysical Research Communications 2018, 499: 1025-1031. PMID: 29634925, DOI: 10.1016/j.bbrc.2018.04.044.Peer-Reviewed Original ResearchConceptsSirt1 KO miceHigh-fat dietInsulin resistanceKO miceLipocalin-2Inflammation-induced insulin resistanceObesity-associated insulin resistanceAnti-inflammatory effectsPrecursor protein levelsWild-type miceHippocampal inflammationWT miceMacrophage infiltrationObese miceLCN2 expressionSIRT1 knockoutType miceHFDAdipose tissueMiceProtein levelsNeuroinflammationSIRT1DietDeficiency
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