Fat-reducing effects of dehydroepiandrosterone involve upregulation of ATGL and HSL expression, and stimulation of lipolysis in adipose tissue

• Published in: Steroids Vol. 77; no. 13; pp. 1359 - 1365
• Main Authors: Karbowska, Joanna, Kochan, Zdzislaw
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 01.11.2012; Elsevier
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue - secretion; Animals; ATGL; Biological and medical sciences; Body Weight - drug effects; Dehydroepiandrosterone - administration & dosage; Dehydroepiandrosterone - pharmacology; DHEA; Epididymis - cytology; Fatty Acids, Nonesterified - blood; Fatty Acids, Nonesterified - secretion; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic - drug effects; Glycerol - metabolism; HSL; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - metabolism; Intra-Abdominal Fat - secretion; Leptin - blood; Lipase - genetics; Lipase - metabolism; Lipolysis - drug effects; Male; Phosphorylation - drug effects; PPAR gamma - genetics; PPARγ; Rat; Rats; Rats, Wistar; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sterol Esterase - genetics; Sterol Esterase - metabolism; Time Factors; Up-Regulation - drug effects; Vertebrates: endocrinology; White adipose tissue; DHEA; HSL; White adipose tissue; Rat; ATGL; PPARγ; Adipose tissue; Rodentia; Lipolysis; Vertebrata; Dehydroepiandrosterone; Mammalia; Animal
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2012.08.002

► DHEA reduces body fat and stimulates adipose tissue triglyceride hydrolysis in rats. ► DHEA upregulates ATGL mRNA and protein expression in rat adipose tissue. ► DHEA increases HSL mRNA levels and Ser660 phosphorylation in rat adipose tissue. ► DHEA promotes lipolysis in adipose tissue by increasing ATGL and HSL expression. ► The effects of DHEA on lipolysis appear to be mediated via PPARγ2 activation. Dehydroepiandrosterone (DHEA) reduces body fat in rodents and humans, and increases glycerol release from isolated rat epididymal adipocytes and human visceral adipose tissue explants. It suggests that DHEA stimulates triglyceride hydrolysis in adipose tissue; however, the mechanisms underlying this action are still unclear. We examined the effects of DHEA on the expression of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), the key enzymes of lipolysis, in rat epididymal white adipose tissue (eWAT). Male Wistar rats were fed a diet containing 0.6% DHEA for 2weeks and eWAT was analyzed for mRNA and protein expression of ATGL and HSL, as well as mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ2) and its downstream target fatty acid translocase (FAT). Glycerol release from eWAT explants and serum free fatty acids (FFA) were also measured. Rats that received DHEA gained less weight, had 23% lower eWAT mass and 31% higher serum FFA levels than controls. Cultured explants of eWAT from DHEA-treated rats released 81% more glycerol than those from control rats. DHEA administration upregulated ATGL mRNA (1.62-fold, P<0.05) and protein (1.78-fold, P<0.05) expression as well as augmented HSL mRNA levels (1.36-fold, P<0.05) and Ser660 phosphorylation of HSL (2.49-fold, P<0.05). PPARγ2 and FAT mRNA levels were also increased in DHEA-treated rats (1.61-fold, P<0.05 and 2.16-fold, P<0.05; respectively). Moreover, ATGL, HSL, and FAT mRNA levels were positively correlated with PPARγ2 expression. This study demonstrates that DHEA promotes lipid mobilization in adipose tissue by increasing the expression and activity of ATGL and HSL. The effects of DHEA appear to be mediated, at least in part, via PPARγ2 activation, which in turn upregulates ATGL and HSL gene expression.