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Gene expression changes in subcutaneous adipose tissue due to Cushing's disease.

Hochberg I, Harvey I, Tran QT, Stephenson EJ, Barkan AL, Saltiel AR, Chandler WF, Bridges D - J. Mol. Endocrinol. (2015)

Bottom Line: Glucocorticoids have major effects on adipose tissue metabolism.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.These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Transcript expression changes in Cushing's disease are less robust after adjusting for obesity. FASN (A), PSMD8 (B), IDH1 (C), and lysosomal (D) transcripts in non-obese and obese Cushing's subjects. * indicates q<0.05.
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fig8: Transcript expression changes in Cushing's disease are less robust after adjusting for obesity. FASN (A), PSMD8 (B), IDH1 (C), and lysosomal (D) transcripts in non-obese and obese Cushing's subjects. * indicates q<0.05.

Mentions: In our small cohort of Cushing's disease subjects, we examined whether some of the dramatic transcriptional changes were modified by the obesity status of the patients (based on a BMI cutoff of 30; Supplementary Tables 4 and 5). We were surprised to note that many genes that had strongly elevated transcripts in non-obese Cushing's disease patients had blunted effects in obese Cushing's disease patients. Some examples of this include FASN, PSMD8 and IDH8 (Fig. 8A, B and C). Among genes that were more strongly induced in obese patients, most of these are involved in lysosomal function, including the cathepsins (CTSB, CTSD, CTSZ), LAPTM5 and LIPA (Fig. 8D). Although the small number of obese and non-obese Cushing's patients in our study makes these provocative observations, preliminary, it is suggestive of both a general reduction of glucocorticoid sensitivity in obese subjects and potentially an underappreciated role of lysosomes in obese patients with elevated cortisol levels.


Gene expression changes in subcutaneous adipose tissue due to Cushing's disease.

Hochberg I, Harvey I, Tran QT, Stephenson EJ, Barkan AL, Saltiel AR, Chandler WF, Bridges D - J. Mol. Endocrinol. (2015)

Transcript expression changes in Cushing's disease are less robust after adjusting for obesity. FASN (A), PSMD8 (B), IDH1 (C), and lysosomal (D) transcripts in non-obese and obese Cushing's subjects. * indicates q<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543687&req=5

fig8: Transcript expression changes in Cushing's disease are less robust after adjusting for obesity. FASN (A), PSMD8 (B), IDH1 (C), and lysosomal (D) transcripts in non-obese and obese Cushing's subjects. * indicates q<0.05.
Mentions: In our small cohort of Cushing's disease subjects, we examined whether some of the dramatic transcriptional changes were modified by the obesity status of the patients (based on a BMI cutoff of 30; Supplementary Tables 4 and 5). We were surprised to note that many genes that had strongly elevated transcripts in non-obese Cushing's disease patients had blunted effects in obese Cushing's disease patients. Some examples of this include FASN, PSMD8 and IDH8 (Fig. 8A, B and C). Among genes that were more strongly induced in obese patients, most of these are involved in lysosomal function, including the cathepsins (CTSB, CTSD, CTSZ), LAPTM5 and LIPA (Fig. 8D). Although the small number of obese and non-obese Cushing's patients in our study makes these provocative observations, preliminary, it is suggestive of both a general reduction of glucocorticoid sensitivity in obese subjects and potentially an underappreciated role of lysosomes in obese patients with elevated cortisol levels.

Bottom Line: Glucocorticoids have major effects on adipose tissue metabolism.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.These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus