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
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
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 regulatorThe Combined Hyperlipidemia Caused by Impaired Wnt-LRP6 Signaling Is Reversed by Wnt3a Rescue
Go GW, Srivastava R, Hernandez-Ono A, Gang G, Smith SB, Booth CJ, Ginsberg HN, Mani A. The Combined Hyperlipidemia Caused by Impaired Wnt-LRP6 Signaling Is Reversed by Wnt3a Rescue. Cell Metabolism 2014, 19: 209-220. PMID: 24506864, PMCID: PMC3920193, DOI: 10.1016/j.cmet.2013.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCells, CulturedFatty LiverHepatocytesHyperlipidemiasLow Density Lipoprotein Receptor-Related Protein-6Mechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MiceModels, BiologicalMultiprotein ComplexesMutationNon-alcoholic Fatty Liver DiseaseTOR Serine-Threonine KinasesWnt3A ProteinConceptsHepatic de novo lipogenesisFatty liver diseaseElevated plasma LDLTreatment of hyperlipidemiaSp1-dependent activationCholesterol biosynthesisDe novo lipogenesisAtherogenic lipid disordersMolecular genetic basisLiver diseaseFatty liverLDL levelsPlasma lipidsTG levelsLipid disordersPlasma TGPlasma LDLNovo lipogenesisHyperlipidemiaCombined HyperlipidemiaGenetic basisWnt coreceptorNonconservative mutationsAltered expressionPrimary hepatocytes