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

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TitleGene expression changes in subcutaneous adipose tissue due to Cushing's disease.
Publication TypeJournal Article
Year of Publication2015
AuthorsHochberg I, Harvey I, Tran QT, Stephenson EJ, Barkan AL, Saltiel AR, Chandler WF, Bridges D
JournalJ Mol Endocrinol
Volume55
Issue2
Pagination81-94
Date Published2015 Oct
ISSN1479-6813
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.

DOI10.1530/JME-15-0119
Alternate JournalJ. Mol. Endocrinol.
PubMed ID26150553
PubMed Central IDPMC4543687
Grant ListR01 DK060591 / DK / NIDDK NIH HHS / United States
U24 DK097153 / DK / NIDDK NIH HHS / United States