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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

Increased glucocorticoids are associated with increased protein degradation and decreased strength. (A) Mouse grip strength (N) assessed at baseline, 4, 8 and 12 weeks of dexamethasone treatment. Muscle atrogene (B) and proteasomal transcript expression changes in gastrocnemius muscles from mice following 1 week of dexamethasone treatment. (C) Proteasomal mRNA levels from subcutaneous adipose tissue of mice treated with dexamethasone for 12 weeks. Proteasomal (D) and protein catabolism (E) transcript expression changes in subcutaneous adipose tissue from Cushing's disease and control subjects. (F) Heatmap of differentially expressed ribosomal transcripts in Cushing's disease and control subjects. * indicates q<0.05.
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fig6: Increased glucocorticoids are associated with increased protein degradation and decreased strength. (A) Mouse grip strength (N) assessed at baseline, 4, 8 and 12 weeks of dexamethasone treatment. Muscle atrogene (B) and proteasomal transcript expression changes in gastrocnemius muscles from mice following 1 week of dexamethasone treatment. (C) Proteasomal mRNA levels from subcutaneous adipose tissue of mice treated with dexamethasone for 12 weeks. Proteasomal (D) and protein catabolism (E) transcript expression changes in subcutaneous adipose tissue from Cushing's disease and control subjects. (F) Heatmap of differentially expressed ribosomal transcripts in Cushing's disease and control subjects. * indicates q<0.05.

Mentions: We found that two major pathways of protein homeostasis are altered in response to glucocorticoids. In concert with reductions in lean body (including muscle) mass (Fig. 2B), we observed substantial muscle weakness in mice treated with dexamethasone (Fig. 6A). In a separate cohort of mice, after 1 week of dexamethasone treatment in skeletal muscle, mRNA levels of the E3 ligases (Atrogin-1 and MuRF1) were induced as was the proteasomal gene PSMD8 (Fig. 6B). These effects did not reach statistical significance due to variability in dexamethasone responsiveness. Similar inductions of the proteasomal genes were observed in the subcutaneous adipose tissue from the cohort of mice treated with dexamethasone for 12 weeks (Fig. 6C).


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)

Increased glucocorticoids are associated with increased protein degradation and decreased strength. (A) Mouse grip strength (N) assessed at baseline, 4, 8 and 12 weeks of dexamethasone treatment. Muscle atrogene (B) and proteasomal transcript expression changes in gastrocnemius muscles from mice following 1 week of dexamethasone treatment. (C) Proteasomal mRNA levels from subcutaneous adipose tissue of mice treated with dexamethasone for 12 weeks. Proteasomal (D) and protein catabolism (E) transcript expression changes in subcutaneous adipose tissue from Cushing's disease and control subjects. (F) Heatmap of differentially expressed ribosomal transcripts in Cushing's disease and control subjects. * indicates q<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Increased glucocorticoids are associated with increased protein degradation and decreased strength. (A) Mouse grip strength (N) assessed at baseline, 4, 8 and 12 weeks of dexamethasone treatment. Muscle atrogene (B) and proteasomal transcript expression changes in gastrocnemius muscles from mice following 1 week of dexamethasone treatment. (C) Proteasomal mRNA levels from subcutaneous adipose tissue of mice treated with dexamethasone for 12 weeks. Proteasomal (D) and protein catabolism (E) transcript expression changes in subcutaneous adipose tissue from Cushing's disease and control subjects. (F) Heatmap of differentially expressed ribosomal transcripts in Cushing's disease and control subjects. * indicates q<0.05.
Mentions: We found that two major pathways of protein homeostasis are altered in response to glucocorticoids. In concert with reductions in lean body (including muscle) mass (Fig. 2B), we observed substantial muscle weakness in mice treated with dexamethasone (Fig. 6A). In a separate cohort of mice, after 1 week of dexamethasone treatment in skeletal muscle, mRNA levels of the E3 ligases (Atrogin-1 and MuRF1) were induced as was the proteasomal gene PSMD8 (Fig. 6B). These effects did not reach statistical significance due to variability in dexamethasone responsiveness. Similar inductions of the proteasomal genes were observed in the subcutaneous adipose tissue from the cohort of mice treated with dexamethasone for 12 weeks (Fig. 6C).

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