I figured I'd jump on the DHEA bandwagon since it's seeming to interest everybody:
Dehydroepiandrosterone up-regulates resistin gene expression in white adipose tissue.
Kochan Z, Karbowska J.
Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland. firstname.lastname@example.org
Dehydroepiandrosterone (DHEA), the most abundant steroid hormone in human blood, is considered to be one of fat-reducing hormones. However, the molecular mechanisms underlying DHEA mode of action in obesity has not been fully clarified. The pivotal role in the maintenance of cellular lipid and energy balance is played by peroxisome proliferator-activated receptor alpha (PPARalpha) which acts as transcriptional activator of numerous genes encoding enzymes involved in fatty acid catabolism. Lately published papers suggest that resistin, a low molecular-weight protein produced by adipose tissue, may act as an inhibitor of adipocyte differentiation and could regulate adipose tissue mass. Recent studies have established that the promoter region of the resistin gene contains several putative PPAR response elements. Since DHEA has been characterized as a peroxisome proliferator able to induce hepatic genes through PPARalpha, we hypothesised that DHEA might affect PPARalpha and, subsequently, resistin gene expression in adipose tissue. In order to test this hypothesis, an experiment was performed comparing PPARalpha and resistin gene expression in white adipose tissue (WAT) of male Wistar rats fed standard or DHEA-supplemented (0.6% (w/w)) diet for 2 weeks. DHEA administration to the rats induced PPARalpha and resistin gene expression in WAT (3- and 2.25-fold, respectively; as determined by real-time transcription-polymerase chain reaction (RT-PCR)); reduced body weight, epididymal adipose tissue mass and decreased serum leptin levels. We propose that DHEA may impact on the transcription of resistin gene through a mechanism involving PPARalpha and that an elevated resistin level may lead to an inhibition of adipogenesis and a decrease in adipose tissue mass.
PMID: 15130511 [PubMed - indexed for MEDLINE]
DHEA administration increases brown fat uncoupling protein 1 levels in obese OLETF rats.
Ryu JW, Kim MS, Kim CH, Song KH, Park JY, Lee JD, Kim JB, Lee KU.
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Poongnap-dong, Songpa-ku, Seoul 138-736, Republic of Korea.
We found that UCP-1 and UCP-3 mRNA expression levels and the UCP-1 protein content in brown adipose tissue (BAT) were reduced in prediabetic OLETF rats than the lean LETO rats. Administration of dehydroepiandrosterone (DHEA) for 17 days induced remarkable weight loss, which was in part attributed to an utilization of ingested energy. DHEA administration significantly increased the levels of BAT UCP-1 and UCP-3 mRNA expression. Among the upstream signals for UCP-1 regulation, expression levels of the beta 3 adrenergic receptor (beta(3)AR) and PPAR gamma coactivator-1 (PGC-1) were significantly decreased in the OLETF rats and increased by DHEA administration. The decreased expression levels of UCP-1 and its upstream regulators, beta(3)AR and PGC-1, in BAT may contribute to inefficient energy utilization and obesity in OLETF rats, which was corrected by DHEA treatment.
PMID: 12659879 [PubMed - indexed for MEDLINE]
Chronic effects of dehydroepiandrosterone on rat adipose tissue metabolism.
Mauriege P, Martel C, Langin D, Lacaille M, Despres JP, Belanger A, Labrie F, Deshaies Y.
Department of Social and Preventive Medicine, and the Department of Anatomy & Physiology, Laval University, Ste-Foy, Quebec, Canada.
The goal of the present study was to examine cellular mechanisms that regulate adipose cell metabolism in ovariectomized (OVX) and intact rats that were subjected to long-term (27 weeks) treatment with dehydroepiandrosterone (DHEA). Forty-eight 16-month-old female rats were divided into 4 groups of 9 to 11 animals (intact, intact-DHEA, OVX, OVX-DHEA). Adipose tissue lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), and cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (cAMP-PDE) activities were determined, and alpha2-, beta1/beta2-, and beta3-adrenoceptors (ARs) were quantified. DHEA did not affect body weight, fat, or in intact rats. The similar retroperitoneal fat pad weight of intact-DHEA rats compared to intact animals was in agreement with the lack of difference in the enzyme activities and AR densities. The increased body weight of OVX rat was paralleled by a greater retroperitoneal adipose tissue mass (P <.01), which was in turn associated with a marked rise in LPL activity (P <.005) and a slight decrease in HSL activity (P <.05) compared to intact animals. OVX-DHEA rats, compared to untreated OVX animals, had a smaller retroperitoneal fat depot, which correlated with a decrease in LPL activity (P <.005) and moderate increase in both HSL activity and beta3-AR (P <.05). DHEA-treatment lowered fasting insulin and triglyceride levels in both intact and OVX rats (P <.05). Plasma testosterone, androsterone, androstenedione, and androstenediol levels were also significantly increased in both intact-DHEA and OVX-DHEA rats compared to untreated animals (P <.0001). These findings suggest that the antiobesity action of DHEA may be related in part to changes in lipase activities and in beta3-AR density, and that it is dependent on the ovarian status of the animal. Copyright 2003, Elsevier Science (USA). All rights reserved.
PMID: 12647261 [PubMed - indexed for MEDLINE]
Dehydroepiandrosterone down-regulates the expression of peroxisome proliferator-activated receptor gamma in adipocytes.
Kajita K, Ishizuka T, Mune T, Miura A, Ishizawa M, Kanoh Y, Kawai Y, Natsume Y, Yasuda K.
The Third Department of Internal Medicine, Gifu University School of Medicine, Tsukasa-machi 40, Gifu 500-8705, Japan.
Dehydroepiandrosterone (DHEA) is expected to have a weight-reducing effect. In this study, we evaluated the effect of DHEA on genetically obese Otsuka Long Evans Fatty rats (OLETF) compared with Long-Evans Tokushima rats (LETO) as control. Feeding with 0.4% DHEA-containing food for 2 wk reduced the weight of sc, epididymal, and perirenal adipose tissue in association with decreased plasma leptin levels in OLETF. Adipose tissue from OLETF showed increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma) protein, which was prevented by DHEA treatment. Further, we examined the effect of DHEA on PPARgamma in primary cultured adipocytes and monolayer adipocytes differentiated from rat preadipocytes. PPARgamma protein level was decreased in a time- and concentration-dependent manner, and DHEA significantly reduced mRNA levels of PPARgamma, adipocyte lipid-binding protein, and sterol regulatory -binding protein, but not CCAAT/enhancer binding protein alpha. DHEA-sulfate also reduced the PPARgamma protein, but dexamethasone, testosterone, or androstenedione did not alter its expression. In addition, treatment with DHEA for 5 d reduced the triglyceride content in monolayer adipocytes. These results suggest that DHEA down-regulates adiposity through the reduction of PPARgamma in adipocytes.
PMID: 12488352 [PubMed - indexed for MEDLINE]
Effect of dehydroepiandrosterone on brown adipose tissue and energy balance in mice.
LeBlanc J, Arvaniti K, Richard D.
Department of Physiology, School of Medicine, Laval University, Quebec City, Canada.
In order to investigate the reported antiobesity action of dehydroepiandrosterone (DHEA), a complete energy balance was made on four groups of mice. Group A was fed the standard Purina diet, group B the same diet to which DHEA was added (0.3%), group C the Purina diet supplemented with palatable high fat food (meat spread), and group D the same diet as group C, to which DHEA was added. Food intake which was larger in groups C and D, was not altered by DHEA treatment. Body weight gain which was comparable for groups A and C, was significantly reduced in the two groups receiving DHEA. The resulting reduced food efficiency caused by DHEA was completely explained by body fat utilization. It was also found that the weight and the protein content of the interscapular brown adipose tissue (BAT) were increased by DHEA treatment suggesting, because of the great thermogenic capacity of this tissue in mice, that it may have been involved in causing the observed reduction in food efficiency. It is also proposed that the action of DHEA may be related to the activation of other tissues such as the liver and muscles. Further investigations are needed to verify this possibility.
PMID: 9660079 [PubMed - indexed for MEDLINE]
DHEA treatment reduces fat accumulation and protects against insulin resistance in male rats.
Han DH, Hansen PA, Chen MM, Holloszy JO.
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
The purpose of this study was to determine whether administration of dehydroepiandrosterone (DHEA) protects male rats against the accumulation of body fat the development of insulin resistance with advancing age. We found that supplementation of the diet with 0.3% DHEA between the ages of 5 months and approximately 25 months resulted in a significantly lower final body weight (DHEA, 593 +/- 18 g vs control, 668 +/- 12 g, p < 0.02), despite no decrease in food intake. Lean body mass was unaffected by the DHEA, and the lower body weight was due to a approximately 25% reduction in body fat. The rate of glucose disposal during a euglycemic, hyperinsulinemic clamp was 30% higher in the DHEA group than in the sedentary controls due to a greater insulin responsiveness. The DHEA administration was as effective in reducing body fat content and maintaining insulin responsiveness as exercise in the form of voluntary wheel running. The DHEA had no significant effect on muscle GLUT4 content. A preliminary experiment provided evidence suggesting that muscle insulin signaling, as reflected in binding of phosphatidylinositol 3-kinase to the insulin receptor substrate-1, was enhanced in the DHEA-treated and wheel running groups as compared to controls. These results provide evidence that DHEA, like exercise, protects against excess fat accumulation and development of insulin resistance in rats.
PMID: 9467418 [PubMed - indexed for MEDLINE]