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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

Dexamethasone treatment results in decreased lean mass and increased fat mass in mice. Weekly body weight (A), lean mass (B), fat mass (C) and percent fat (D) from control (black) and dexamethasone (red) treated mice. (E) Average food consumption per mouse per day. (F) Insulin tolerance test. Following a 6-h fast, insulin (1 mU/g) was administered via i.p. injection, and blood glucose was measured at baseline and the indicated time post injection. (G) Inguinal (IWAT) and epididymal (EWAT) fat pad weights, for right fat pads only. *P<0.05.
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fig2: Dexamethasone treatment results in decreased lean mass and increased fat mass in mice. Weekly body weight (A), lean mass (B), fat mass (C) and percent fat (D) from control (black) and dexamethasone (red) treated mice. (E) Average food consumption per mouse per day. (F) Insulin tolerance test. Following a 6-h fast, insulin (1 mU/g) was administered via i.p. injection, and blood glucose was measured at baseline and the indicated time post injection. (G) Inguinal (IWAT) and epididymal (EWAT) fat pad weights, for right fat pads only. *P<0.05.

Mentions: To validate the gene expression changes observed in human subjects, we treated C67BL/6J mice with dexamethasone, a synthetic glucocorticoid, in their drinking water to mimic the systemic effects of cortisol overproduction. These mice had an initial catabolic phase in which their body weight was rapidly reduced (Fig. 2A), an effect that was primarily due to a reduction in lean body mass (Fig. 2B). This is consistent with previously reported effects of glucocorticoids on muscle atrophy (Pleasure et al. 1970). After ∼5 weeks, we observed an elevation in both total fat mass and percent adiposity in the dexamethasone-treated mice (Fig. 2C and D). We did not detect any differences in food intake between the groups throughout the study (Fig. 2E). To evaluate insulin sensitivity, we performed insulin tolerance tests on these mice after 12 weeks of dexamethasone treatment and found that while they had reduced fasting glucose at this stage, they were resistant to insulin-induced reductions in blood glucose (Fig. 2E). On sacrifice after 12 weeks of dexamethasone treatment, the adipose tissue was dissected and weighed. As shown in Fig. 2F, we observed elevated subcutaneous fat mass in dexamethasone-treated animals.


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)

Dexamethasone treatment results in decreased lean mass and increased fat mass in mice. Weekly body weight (A), lean mass (B), fat mass (C) and percent fat (D) from control (black) and dexamethasone (red) treated mice. (E) Average food consumption per mouse per day. (F) Insulin tolerance test. Following a 6-h fast, insulin (1 mU/g) was administered via i.p. injection, and blood glucose was measured at baseline and the indicated time post injection. (G) Inguinal (IWAT) and epididymal (EWAT) fat pad weights, for right fat pads only. *P<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Dexamethasone treatment results in decreased lean mass and increased fat mass in mice. Weekly body weight (A), lean mass (B), fat mass (C) and percent fat (D) from control (black) and dexamethasone (red) treated mice. (E) Average food consumption per mouse per day. (F) Insulin tolerance test. Following a 6-h fast, insulin (1 mU/g) was administered via i.p. injection, and blood glucose was measured at baseline and the indicated time post injection. (G) Inguinal (IWAT) and epididymal (EWAT) fat pad weights, for right fat pads only. *P<0.05.
Mentions: To validate the gene expression changes observed in human subjects, we treated C67BL/6J mice with dexamethasone, a synthetic glucocorticoid, in their drinking water to mimic the systemic effects of cortisol overproduction. These mice had an initial catabolic phase in which their body weight was rapidly reduced (Fig. 2A), an effect that was primarily due to a reduction in lean body mass (Fig. 2B). This is consistent with previously reported effects of glucocorticoids on muscle atrophy (Pleasure et al. 1970). After ∼5 weeks, we observed an elevation in both total fat mass and percent adiposity in the dexamethasone-treated mice (Fig. 2C and D). We did not detect any differences in food intake between the groups throughout the study (Fig. 2E). To evaluate insulin sensitivity, we performed insulin tolerance tests on these mice after 12 weeks of dexamethasone treatment and found that while they had reduced fasting glucose at this stage, they were resistant to insulin-induced reductions in blood glucose (Fig. 2E). On sacrifice after 12 weeks of dexamethasone treatment, the adipose tissue was dissected and weighed. As shown in Fig. 2F, we observed elevated subcutaneous fat mass in dexamethasone-treated animals.

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