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RESEARCH PRODUCT
Insulin Dissociates the Effects of Liver X Receptor on Lipogenesis, Endoplasmic Reticulum Stress, and Inflammation
Rosanne M. CrookeJianguo WangXiaowei SunJean-paul Pais De BarrosAbhiruchi J MehtaDavid MassonJi MiaoMary E. HaasSudha B. BiddingerMark J. GrahamMasanori Aikawasubject
0301 basic medicinemedicine.medical_treatmentLipid-metabolismResistanceBiochemistryHepatitisMESH: HepatitisMESH: Endoplasmic Reticulum Stresspolycyclic compoundsInsulinGene-expressionPhospholipidsLiver X ReceptorsMice KnockoutbiologyMESH : Gene Expression RegulationFatty-acid synthesisfood and beveragesEndoplasmic Reticulum StressOrphan Nuclear ReceptorsCultured-cellsLipidsMESH: Gene Expression RegulationMESH : Endoplasmic Reticulum StressMessenger-rnaLiverMESH: Orphan Nuclear ReceptorsGene Knockdown TechniquesLipogenesisFemalelipids (amino acids peptides and proteins)Signal Transductionliver X receptormedicine.medical_specialtyLxr-alphaMice Transgenicdigestive systemPhospholipid transfer proteinGene Expression Regulation Enzymologic03 medical and health sciencesInsulin resistanceMESH : HepatitisLysophosphatidylcholine acyltransferaseInternal medicinemedicineAnimals[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular BiologyLiver X receptorMolecular Biology[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular BiologyCrosses GeneticLipogenesisEndoplasmic reticulumInsulinElement-binding protein-1cMESH : LiverCell Biologymedicine.diseaseMESH : Orphan Nuclear ReceptorsReceptor InsulinMice Inbred C57BLInsulin receptor030104 developmental biologyEndocrinologyDiabetes Mellitus Type 2Gene Expression RegulationNuclear receptorbiology.proteinUnfolded protein responseInsulin ResistanceMESH: Liverdescription
IF 4.258; International audience; Diabetes is characterized by increased lipogenesis as well as increased endoplasmic reticulum (ER) stress and inflammation. The nuclear hormone receptor liver X receptor (LXR) is induced by insulin and is a key regulator of lipid metabolism. It promotes lipogenesis and cholesterol efflux, but suppresses endoplasmic reticulum stress and inflammation. The goal of these studies was to dissect the effects of insulin on LXR action. We used antisense oligonucleotides to knock down Lxr alpha in mice with hepatocytespecific deletion of the insulin receptor and their controls. We found, surprisingly, that knock-out of the insulin receptor and knockdown of Lxr alpha produced equivalent, non-additive effects on the lipogenic genes. Thus, insulin was unable to induce the lipogenic genes in the absence of Lxr alpha, and LXR alpha was unable to induce the lipogenic genes in the absence of insulin. However, insulin was not required for LXR alpha to modulate the phospholipid profile, or to suppress genes in the ER stress or inflammation pathways. These data show that insulin is required specifically for the lipogenic effects of LXR alpha and that manipulation of the insulin signaling pathway could dissociate the beneficial effects of LXR on cholesterol efflux, inflammation, and ER stress from the negative effects on lipogenesis.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-01-15 |