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 insulinSteatosisLiverCirrhosisSteatohepatitis
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
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