title: Gene expression changes in subcutaneous adipose tissue due to Cushing's disease.
abstract: Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on the subcutaneous adipose tissue from patients with Cushing's disease (n=5) compared to patients with nonfunctioning pituitary adenomas (n=11). We found a higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as a decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids.
authors.affiliation: Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA i_hochberg@rambam.health.gov.il dbridge9@uthsc.edu.
authors.forename: Irit
authors.initials: I
authors.lastname: Hochberg
authors.affiliation: Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA.
authors.forename: Innocence
authors.initials: I
authors.lastname: Harvey
authors.affiliation: Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA.
authors.forename: Quynh T
authors.initials: QT
authors.lastname: Tran
authors.affiliation: Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA.
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Stephenson
authors.affiliation: Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA.
authors.forename: Ariel L
authors.initials: AL
authors.lastname: Barkan
authors.affiliation: Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Saltiel
authors.affiliation: Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Chandler
authors.affiliation: Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA Institute of EndocrinologyDiabetes and Metabolism, Rambam Health Care Campus, Haifa, IsraelLife Science InstituteUniversity of Michigan, Ann Arbor, MI, USAPhysiologyUTHSC, Memphis, TN, USAPreventive MedicineUTHSC, Memphis, TN, USAInternal MedicineUniversity of Michigan, Ann Arbor, MI USANeurosurgeryUniversity of Michigan, Ann Arbor, MI USAPediatricsUTHSC, Memphis, TN, USA i_hochberg@rambam.health.gov.il dbridge9@uthsc.edu.
authors.forename: Dave
authors.initials: D
authors.lastname: Bridges
mesh_terms: D000818:Animals; D001483:Base Sequence; D002518:Ceramides / Q000032:analysis; D003480:Cushing Syndrome / Q000235:genetics* / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D050155:Lipogenesis / Q000235:genetics; D008066:Lipolysis / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D010911:Pituitary Neoplasms / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D050151:Subcutaneous Fat / Q000166:cytology* / Q000378:metabolism*
chemical_list: D002518:Ceramides; D007328:Insulin; D012333:RNA, Messenger; D003907:Dexamethasone; D005947:Glucose
keywords: Cushing's syndrome; RNA sequencing; glucocorticoid; insulin resistance; lipogenesis; lipolysis; transcriptome