2022
Dyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice
Bhat N, Narayanan A, Fathzadeh M, Kahn M, Zhang D, Goedeke L, Neogi A, Cardone RL, Kibbey RG, Fernandez-Hernando C, Ginsberg HN, Jain D, Shulman G, Mani A. Dyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice. Journal Of Clinical Investigation 2022, 132: e153724. PMID: 34855620, PMCID: PMC8803348, DOI: 10.1172/jci153724.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisNonalcoholic steatohepatitisInsulin resistanceHepatic lipogenesisElevated de novo lipogenesisNonalcoholic fatty liver diseaseFatty liver diseaseLiver of patientsHepatic glycogen storageHigh-sucrose dietHepatic insulin resistanceFatty acid uptakeMetabolic syndromeLiver diseaseHepatic steatosisTriacylglycerol secretionNovo lipogenesisHepatic insulinTherapeutic targetImpaired activationAcid uptakeGlycogen storageMouse liverLiverLipogenesis
2019
CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation
Esteghamat F, Broughton JS, Smith E, Cardone R, Tyagi T, Guerra M, Szabó A, Ugwu N, Mani MV, Azari B, Kayingo G, Chung S, Fathzadeh M, Weiss E, Bender J, Mane S, Lifton RP, Adeniran A, Nathanson MH, Gorelick FS, Hwa J, Sahin-Tóth M, Belfort-DeAguiar R, Kibbey RG, Mani A. CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation. Nature Genetics 2019, 51: 1233-1243. PMID: 31358993, PMCID: PMC6675645, DOI: 10.1038/s41588-019-0470-3.Peer-Reviewed Original ResearchConceptsEarly-onset atherosclerosisMetabolic syndromeMetabolic syndrome traitsWhole-exome sequence analysisAttractive therapeutic targetPlatelet hyperactivationInsulin levelsPlasma insulinPlasma levelsInsulin sensitivityInsulin secretionTherapeutic targetPlatelet activationDisease mechanismsSyndrome traitsAtherosclerosisFunction mutationsSyndromeNovel lossInsulinMutationsSecretion
2018
The interplay of canonical and noncanonical Wnt signaling in metabolic syndrome
Abou Ziki M, Mani A. The interplay of canonical and noncanonical Wnt signaling in metabolic syndrome. Nutrition Research 2018, 70: 18-25. PMID: 30049588, PMCID: PMC6320319, DOI: 10.1016/j.nutres.2018.06.009.Peer-Reviewed Original ResearchConceptsMetabolic syndromeLow density lipoprotein clearanceVascular smooth muscle proliferationEnd-organ complicationsCanonical WntSmooth muscle proliferationLow-density lipoproteinDe novo lipogenesisInsulin receptor expressionTranscription factor 7Growth factor βRas homolog gene family member AExtracellular matrix depositionCardiometabolic abnormalitiesLiver inflammationFamily member AInsulin resistanceLipoprotein clearanceLiver fatHepatic fibrosisSevere manifestationsLDL receptor-related protein 6Receptor expressionCardiovascular diseaseMuscle proliferation
2017
Wnt signaling, a novel pathway regulating blood pressure? State of the art review
Ziki M, Mani A. Wnt signaling, a novel pathway regulating blood pressure? State of the art review. Atherosclerosis 2017, 262: 171-178. PMID: 28522145, PMCID: PMC5508596, DOI: 10.1016/j.atherosclerosis.2017.05.001.Peer-Reviewed Original ResearchConceptsBP regulationType 2 diabetes mellitusBlood pressure targetsPathogenesis of hypertensionTight BP controlTherapy of hypertensionField of hypertensionReview of PubMedDrug developmentNovel drug developmentAntihypertensive TrialBP controlDifferent metabolic profilesUnique molecular pathwaysPressure targetsBlood pressureDiabetes mellitusMetabolic syndromePatient populationHypertensionStudy populationHeterogeneous diseaseReference listsPrecision Medicine InitiativeContribution of Wnt
2015
The Protective Effect of Transcription Factor 7‐Like 2 Risk Allele rs7903146 against Elevated Fasting Plasma Triglyceride in Type 2 Diabetes: A Meta‐Analysis
Wang S, Song K, Srivastava R, Fathzadeh M, Li N, Mani A. The Protective Effect of Transcription Factor 7‐Like 2 Risk Allele rs7903146 against Elevated Fasting Plasma Triglyceride in Type 2 Diabetes: A Meta‐Analysis. Journal Of Diabetes Research 2015, 2015: 468627. PMID: 26576435, PMCID: PMC4631899, DOI: 10.1155/2015/468627.Peer-Reviewed Original ResearchConceptsType 2 diabetesTranscription factor 7Rs7903146 variantNondiabetic subjectsMinor alleleHeterozygote comparison modelHDL-C levelsLower plasma triglyceride levelsTCF7L2 rs7903146 polymorphismFactor 7Plasma lipid levelsPlasma triglyceride levelsVariant rs7903146Metabolic syndromeRs7903146 polymorphismPlasma lipidsTG levelsTriglyceride levelsPlasma triglyceridesLipid levelsProtective effectLower riskElectronic databasesType 2Meta-AnalysisNew targets to treat obesity and the metabolic syndrome
Martin KA, Mani MV, Mani A. New targets to treat obesity and the metabolic syndrome. European Journal Of Pharmacology 2015, 763: 64-74. PMID: 26001373, PMCID: PMC4573317, DOI: 10.1016/j.ejphar.2015.03.093.Peer-Reviewed Original ResearchConceptsMetabolic syndromeCardiovascular diseaseGlucagon-like peptide-1 receptor agonistsPancreatic lipase inhibitor orlistatSingle CVD risk factorPeptide-1 receptor agonistsCVD risk factorsEpidemic of obesityLong-term treatmentType 2 diabetesLipase inhibitor orlistatDipeptidyl peptidase IV inhibitorsAnti-diabetic drugsFuture drug developmentTruncal obesitySerotonergic drugsReceptor agonistRisk factorsMelanocortin systemObesityMetabolic traitsSyndromeMetabolic profileIV inhibitorsNew targets
2014
Wnt signaling, de novo lipogenesis, adipogenesis and ectopic fat
Song K, Wang S, Mani M, Mani A. Wnt signaling, de novo lipogenesis, adipogenesis and ectopic fat. Oncotarget 2014, 5: 11000-11003. PMID: 25526027, PMCID: PMC4294374, DOI: 10.18632/oncotarget.2769.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseFatty liver diseaseDe novo lipogenesisEctopic fatLiver diseaseNovo lipogenesisMesenchymal stem cellsElevated plasma lipidsHigher plasma triglyceridesMetabolic syndromePlasma lipidsCoronary arteryInsulin resistancePlasma triglyceridesLoss of functionWnt coreceptor LRP6Diverse congenitalPertinent findingsFunction mutationsAdipogenesisCoreceptor LRP6DiseaseStem cellsLipogenesisMajor regulator