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

• Published in: Obesity (Silver Spring, Md.) Md.), 2007-05, Vol.15 (5), p.1107-1132
• Main Authors: Bolduc, Carl, Yoshioka, Mayumi, St-Amand, Jonny
• Format: Article
• Language: English
• Subjects: Abdomen; Adipocytes; adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - physiology; Androgens; animal models; Animals; Antigens; biochemical pathways; Body fat; carbohydrate metabolism; Cardiovascular disease; Cell cycle; Coronary vessels; dietary supplements; Dihydrotestosterone - pharmacology; Endocrinology; Fructose-Bisphosphate Aldolase; Gene expression; gene expression regulation; Gene Expression Regulation - drug effects; genetic markers; Genomics; Glycolysis - genetics; Hormones; Kinases; lipid metabolism; Malate Dehydrogenase - genetics; Male; males; messenger RNA; Metabolism; Metabolites; Mice; Mice, Inbred C57BL; molecular genetics; Obesity; Oncology; Orchiectomy; Physiology; Polymerase chain reaction; Proteins; Pyruvate Kinase - genetics; Research methodology; sex hormones; synthetic androgens; Transcription, Genetic; transcriptome; transcriptomics; Vein & artery diseases
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1038/oby.2007.623

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 ~150,000 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.