2020
Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis
Perry RJ, Zhang D, Guerra MT, Brill AL, Goedeke L, Nasiri AR, Rabin-Court A, Wang Y, Peng L, Dufour S, Zhang Y, Zhang XM, Butrico GM, Toussaint K, Nozaki Y, Cline GW, Petersen KF, Nathanson MH, Ehrlich BE, Shulman GI. Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis. Nature 2020, 579: 279-283. PMID: 32132708, PMCID: PMC7101062, DOI: 10.1038/s41586-020-2074-6.Peer-Reviewed Original ResearchConceptsHepatic steatosisType 2Nonalcoholic fatty liver diseaseDiet-induced hepatic steatosisFatty liver diseasePlasma glucagon concentrationsHepatic adipose triglyceride lipaseHepatic acetyl-CoA contentHepatic glucose productionRatio of insulinHepatic glucose metabolismInositol triphosphate receptorAdipose triglyceride lipaseMitochondrial oxidationMitochondrial fat oxidationGlucose intoleranceLiver diseaseGlucagon concentrationsInsulin resistancePortal veinAcetyl-CoA contentHepatic lipolysisGlucagon biologyGlucose metabolismKnockout mice
2018
Leptin Mediates a Glucose-Fatty Acid Cycle to Maintain Glucose Homeostasis in Starvation
Perry RJ, Wang Y, Cline GW, Rabin-Court A, Song JD, Dufour S, Zhang XM, Petersen KF, Shulman GI. Leptin Mediates a Glucose-Fatty Acid Cycle to Maintain Glucose Homeostasis in Starvation. Cell 2018, 172: 234-248.e17. PMID: 29307489, PMCID: PMC5766366, DOI: 10.1016/j.cell.2017.12.001.Peer-Reviewed Original Research
2017
Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Ferrandino G, Kaspari RR, Spadaro O, Reyna-Neyra A, Perry RJ, Cardone R, Kibbey RG, Shulman GI, Dixit VD, Carrasco N. Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e9172-e9180. PMID: 29073114, PMCID: PMC5664516, DOI: 10.1073/pnas.1707797114.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseDe novo lipogenesisAdipose tissue lipolysisHepatic insulin resistanceThyroid hormonesHypothyroid miceImpaired suppressionInsulin resistanceTissue lipolysisInsulin secretionHigh thyroid-stimulating hormone levelsRegulation of THThyroid-stimulating hormone levelsLipid utilizationFatty liver diseaseSerum glucose levelsEndogenous glucose productionLow thyroid hormoneFatty acidsHepatic lipid utilizationLiver diseaseSevere hypothyroidismHormone levelsProfound suppressionGlucose levels
2015
Hepatic Acetyl CoA Links Adipose Tissue Inflammation to Hepatic Insulin Resistance and Type 2 Diabetes
Perry RJ, Camporez JP, Kursawe R, Titchenell PM, Zhang D, Perry CJ, Jurczak MJ, Abudukadier A, Han MS, Zhang XM, Ruan HB, Yang X, Caprio S, Kaech SM, Sul HS, Birnbaum MJ, Davis RJ, Cline GW, Petersen KF, Shulman GI. Hepatic Acetyl CoA Links Adipose Tissue Inflammation to Hepatic Insulin Resistance and Type 2 Diabetes. Cell 2015, 160: 745-758. PMID: 25662011, PMCID: PMC4498261, DOI: 10.1016/j.cell.2015.01.012.Peer-Reviewed Original ResearchConceptsHepatic glucose productionWhite adipose tissueHepatic insulin resistanceInsulin resistanceImpaired insulin-mediated suppressionAdipose tissue inflammationIL-6 neutralizationIL-6 infusionType 2 diabetesInsulin-mediated suppressionSuppression of lipolysisAdipose triglyceride lipaseTissue inflammationAdipose tissueType 2Fed ratsGlucose productionGenetic ablationInsulin's abilityAcetyl CoATriglyceride lipaseInsulin signalingRatsMetabolomics approachInsulin