Original Article

Obesity (2007) 15, 1107–1132; doi: 10.1038/oby.2007.623

Transcriptomic Characterization of the Long-term Dihydrotestosterone Effects in Adipose Tissue*

Carl Bolduc*, Mayumi Yoshioka* and Jonny St-Amand*

*Department of Anatomy and Physiology, Université Laval, Functional Genomics Laboratory, Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, Quebec City, Quebec, Canada.

Correspondence: Jonny St-Amand Functional Genomics Laboratory, Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, 2705 Boulevard Laurier, Quebec City, Quebec, G1V 4G2 Canada. E-mail: Jonny.St-Amand@crchul.ulaval.ca

*The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 28 July 2006; Revised  0000; Accepted 16 November 2006.

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Abstract

Objective: To study the long-term transcriptomic effects of dihydrotestosterone (DHT) in adipose tissue. Fat distribution is regulated by sexual hormones. It is still unclear if androgens are promoting or reducing intra-abdominal fat accumulation.

Research Methods and Procedures: Retroperitoneal adipose tissue were isolated from each group of gonadectomized (GDX) C57BL6 male mice treated with vehicle or DHT for 21 days. Serial analysis of gene expression (SAGE) was performed to generate approx150,000 SAGE tags from each sample.

Results: Among the numerous genes regulated by DHT, transcripts involved in glycolysis, such as aldolase 1 A isoform and pyruvate kinase muscle as well as lipogenic transcripts, such as malic enzyme supernatant and ELOVL family member 6 elongation of long chain fatty acids were down-regulated by androgen supplementation. In contrast, transcripts involved in lipolysis and fatty acid oxidation, such as carboxylesterase 3, acetyl-coenzyme A acyltransferase 1, 3-ketoacyl-CoA thiolase B and enoyl-coenzyme A hydratase/3-hydroxyacyl coenzyme A dehydrogenase were up-regulated by DHT. Pro-apoptotic transcripts such as cell death-inducing DFFA-like effector c, BCL2/adenovirus E1B 19 kDa-interacting protein 1 NIP3 and -interacting protein 3-like were up-regulated by DHT, whereas transcripts involved in promotion of cell cycle such as cyclin D2 were down-regulated by DHT.

Discussion: These results suggest that chronic androgen treatment may help to improve metabolic profile by regulating various critical pathways involved in adipose tissue physiology. In addition, several genes associated with a healthier metabolic profile, such as adiponectin and CD36 antigen, were up-regulated by 21 days of DHT treatment.

Keywords:

molecular genetics, sex hormones, lipid metabolism, gene expression

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