2023
Dysregulation of Lipid and Glucose Metabolism in Nonalcoholic Fatty Liver Disease
Bhat N, Mani A. Dysregulation of Lipid and Glucose Metabolism in Nonalcoholic Fatty Liver Disease. Nutrients 2023, 15: 2323. PMID: 37242206, PMCID: PMC10222271, DOI: 10.3390/nu15102323.Peer-Reviewed Original ResearchConceptsFatty liver diseaseLiver diseaseHepatocellular carcinomaAlcoholic fatty liver diseaseNonalcoholic fatty liver diseaseInsulin-resistant liverDiet-induced steatosisCurrent therapeutic effortsDysregulation of lipidAccumulation of lipidsHepatic fatPrevalent conditionSevere stagesGenetic predispositionGlucose metabolismHealthcare costsEconomic burdenTherapeutic effortsDiseaseNAFLDCanonical insulinSteatosisLiverCirrhosisSteatohepatitisA Form of Metabolic-Associated Fatty Liver Disease Associated with a Novel LIPA Variant
Anushiravani A, Khamirani H, Mohamadkhani A, Mani A, Dianatpour M, Malekzadeh R. A Form of Metabolic-Associated Fatty Liver Disease Associated with a Novel LIPA Variant. Archives Of Iranian Medicine 2023, 26: 86-91. PMID: 37543928, PMCID: PMC10685898, DOI: 10.34172/aim.2023.14.Peer-Reviewed Original ResearchConceptsFatty liver diseaseVibration-controlled transient elastographyLiver diseaseLysosomal acid lipaseHomozygous missense variantCholesteryl ester storage diseaseWhole-exome sequencingMissense variantsLiver Disease AssociatedBody mass indexRoutine laboratory testsHigh cholesterol levelsSanger sequencingIranian familyFamily membersNovel missense variantLiPA resultsNASH cirrhosisSevere dyslipidemiaFatty liverMass indexDisease AssociatedCholesterol levelsTransient elastographyCirrhosis
2022
Complex regulation of fatty liver disease
Ginsberg HN, Mani A. Complex regulation of fatty liver disease. Science 2022, 376: 247-248. PMID: 35420931, PMCID: PMC9619413, DOI: 10.1126/science.abp8276.Peer-Reviewed Original ResearchTCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut‐liver crosstalk
Bhat N, Esteghamat F, Chaube BK, Gunawardhana K, Mani M, Thames C, Jain D, Ginsberg HN, Fernandes‐Hernando C, Mani A. TCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut‐liver crosstalk. The FASEB Journal 2022, 36: e22185. PMID: 35133032, PMCID: PMC9624374, DOI: 10.1096/fj.202101607r.Peer-Reviewed Original ResearchConceptsGut-liver crosstalkBile synthesisDiet-induced fatty liver diseaseSmall intestineHepatic bile saltIntestinal lipid uptakePlasma bile saltsFatty liver diseaseTreatment of NASHColorectal cancer cellsBile saltsConditional knockout modelHuman NASHFatty liverLiver diseaseFXR activationClinical trialsEnterohepatic circulationTranscription factor TCF4Fl/Hepatic levelsBile acidsEndocrine regulatorLipid uptakeIntestinal epitheliumDyrk1b 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
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