Dehydroepiandrosterone-sulfate (DHEAS) reduces adipocyte hyperplasia associated with feeding rats a high-fat diet

Lea-Currie, Y. Renee; Wen, Ping; McIntosh, Michael

doi:10.1038/sj.ijo.0800516

Cited by 31 publications

(22 citation statements)

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“…16 This hormone has been accredited with an anti-obesity action as well as a protective role against associated metabolic problems. 17,18 The ®ndings that TNF-a values in the obese population were above the normal range coincides with various studies which indicate that the synthesis and secretion of this cytokine increases with obesity 19,20 and can be interpreted as an adaptation mechanism for the prevention of future weight gain. 21 Serum leptin values were far above normal ranges in both sexes, con®rming the results of other authors, which indicate that obese individuals have a mean leptin concentration in serum approximately four times higher than individuals of normal weight.…”

Section: General Characteristicsmentioning

confidence: 67%

Endocrine, metabolic and nutritional factors in obesity and their relative significance as studied by factor analysis

et al. 2001

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OBJECTIVE:To evaluate different aspects of obesity, such as body fat distribution, plasma hormone and lipid pro®les, adipose tissue composition and dietary intake in an obese population in order to identify the most important factors that contribute to obesity. DESIGN: Eighty-®ve obese subjects, 30 men and 55 women (age, 30 ± 70 y; body mass index (BMI), 27 ± 35 kgam 2 ), were studied using anthropometric measurements, computed tomography, adipose tissue composition, serum hormone and lipid pro®les and nutritional evaluations. To determine to what extent individual factors contributed to the general process of obesity, the data were subjected to a factor analysis. RESULTS: Three patterns of anthropometric and computed tomography data emerged that accounted for 69% of the variance. Factor 1 de®ned abdominal obesity and explained 30% of the total variance, factor 2 (gynoid obesity) accounted for 26%; and factor 3 (subcutaneous fat) explained 13% of the total variance. When other factors associated with obesity, such as lipid pro®le, hormonal pro®le and fat composition, were introduced, obesity itself, especially abdominal obesity, remained the principal factor, accounting for 23% of total variability. All factors were of secondary importance when dietary characteristics were introduced. In the overall factor analysis, more than 40% of the variability in obesity was related to dietary habits, particularly fat intake, followed by energy and saturated fatty acids intake. CONCLUSION: Even though obesity is a multifactorial phenomenon, the results suggest that dietary intake, especially fat intake, is the most important factor contributing to obesity. Secondary factors include endocrine and metabolic factors.

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Section: General Characteristicsmentioning

confidence: 67%

Endocrine, metabolic and nutritional factors in obesity and their relative significance as studied by factor analysis

et al. 2001

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“…These Wistar rats were housed individually in an animal facility under controlled conditions (12:12-h light-dark cycle). To induce obesity and hyperglycemia, the rats were allowed water ad libitum and placed on a purified high-sucrose diet (68% of kcal from sucrose, 20% from protein, and 12% from fat) for 14 wk, which was based on a previous study with minor modifications (9,17). After 14 wk, the obese animals were randomly assigned to one of three groups: control (n ϭ 10), DHEA administration (n ϭ 10), or exercise training (n ϭ 10).…”

Section: Methodsmentioning

confidence: 99%

Increased muscular dehydroepiandrosterone levels are associated with improved hyperglycemia in obese rats

Sato

Iemitsu

Aizawa

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Sato K, Iemitsu M, Aizawa K, Mesaki N, Fujita S. Increased muscular dehydroepiandrosterone levels are associated with improved hyperglycemia in obese rats. Am J Physiol Endocrinol Metab 301: E274-E280, 2011. First published February 1, 2011 doi:10.1152/ajpendo.00564.2010.-This study was undertaken to assess the effects of dehydroepiandrosterone (DHEA) administration and exercise training on muscular DHEA and 5␣-dihydrotestosterone (DHT) levels and hyperglycemia in dietinduced obese and hyperglycemic rats. After 14 wk of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of three 6-wk regimens: control, DHEA treatment, or exercise training (running at 25 m/min for 1 h, 5 days/wk; n ϭ 10 each group). Results indicate that either 6 wk of DHEA treatment or exercise training significantly attenuated serum insulin and fasting glucose levels compared with the control group. Plasma and muscle concentrations of DHEA and DHT and expression levels of 5␣-reductase were significantly higher in the DHEA-treated and exercise-training groups. Moreover, both DHEA administration and exercise training upregulated GLUT4 translocation with concomitant increases in protein kinase B and protein kinase C/ phosphorylation. Muscle DHEA and DHT concentrations closely correlated with blood glucose levels (DHEA treatment: r ϭ Ϫ0.68, P Ͻ 0.001; exercise training: r ϭ Ϫ0.65, P Ͻ 0.001), serum insulin levels, and activation of the GLUT4-regulated signaling pathway. Thus, increased levels of muscle sex steroids may contribute to improved fasting glucose levels via upregulation of GLUT4-regulated signaling in diet-induced obesity and hyperglycemia. muscle glucose metabolism; exercise; sex steroid hormone EPIDEMIOLOGIC, EXPERIMENTAL, AND CLINICAL EVIDENCE has demonstrated that diet-induced obesity and weight gain are closely associated with increased risk of diabetes morbidity, including cardiovascular diseases, hypertension, and dyslipidemia (9). Obesity triples the diabetes morbidity that results from impaired glucose metabolism, such as decreased uptake and utilization in skeletal muscle (9, 10). These effects are mediated, in part, by impaired regulation of glucose transporter-4 (GLUT4); binding of insulin receptor substrate (IRS) is inhibited in skeletal muscle, which downregulates the activities of protein kinase B (Akt) and/or protein kinase C/ (PKC/) via phosphatidylinositol 3-kinase (PI 3-kinase) (14).Dehydroepiandrosterone (DHEA) and its sulfate derivate (DHEA-S) are precursors of sex steroid hormones. DHEA is converted to testosterone and 5␣-dihydrotestosterone (DHT) by 3␤-hydroxysteroid dehydrogenase (HSD), 17␤-HSD, and 5␣-reductase. DHEA is most abundantly localized in blood before it is used by target tissues. Several reports have shown that short-term DHEA administration (2 wk) induces an acute decrease in blood glucose levels in type 2 diabetic mice (4 -7). Recently, we used cultured muscle cells to demonstrate that DHEA induced local production of testosterone, whereas DHT increased the activation of the G...

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“…Furthermore, recent studies by our group indicate that DHEAS is more effective than DHEA in reducing adipose tissue mass and cellularity in rats. 16,17 We have preliminary data suggesting that DHEA directly alters the growth of adipose tissue. We found that treating 3T3-L1 preadipocytes 18 and stromalvascular (SV) cells from adipose tissue of pigs and rats 19 with DHEA attenuated cellular proliferation and differentiation.…”

Section: Introductionmentioning

confidence: 99%

Dehydroepiandrosterone alters the growth of stromal vascular cells from human adipose tissue

et al. 1999

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OBJECTIVE: The purpose of this study was to determine if the antiobesity actions of dehydroepiandrosterone (DHEA) observed in vivo are due to an in¯uence on the proliferation and differentiation of primary cultures of stromal-vascular (SV) cells isolated from human adipose tissue. DESIGN: SV cells were isolated from subcutaneous adipose tissue obtained from a young adult female undergoing elective liposuction. For the proliferation assay (Experiment 1), cultures were fed proliferation media containing 0, 5, 25 or 100 mM DHEA for 3 d. At the end of this treatment period, cultures were either prepared for counting or for determining their metabolic activity using the Alamar Blue staining procedure. For the differentiation assays (Experiment 2), cultures were fed differentiation media containing 0, 25 or 50 mM DHEA for 20 d. At the end of this treatment period, cultures were either prepared for lipid staining using Oil Red O or for marker enzyme analysis (glycerol-3-phosphate dehydrogenase activity; GPDH). To determine if the stimulatory effects of DHEA on SV cell differentiation were dependent on the presence of thiazolidinediones (Experiment 3), cultures of differentiating SV cells were incubated in the presence and absence of BRL 49653 and either 0, 25 or 50 mM DHEA. RESULTS: In Experiment 1, cultures treated with 25 and 100 mM DHEA had fewer cells than cultures treated with either 0 or 5 mM DHEA. Alamar Blue staining decreased as the level of DHEA in the cultures increased. In Experiment 2, cultures treated with DHEA had more lipid and GPDH activity than control cultures. In Experiment 3, cultures treated with BRL 49653 had more triglyceride than cultures treated without BRL 49653. Likewise, cultures treated with DHEA had more triglyceride than their non-DHEA controls. Regardless of the BRL status, cultures supplemented with DHEA had more triglyceride than control cultures. CONCLUSION: These data suggest that in cultures of SV cells from human adipose tissue, DHEA supplementation attenuates proliferation and enhances differentiation. These data support the hypothesis that DHEA directly attenuates preadipocyte proliferation in humans as we previously demonstrated in primary cultures of pig and rat SV cells and in cultures of 3T3-L1 preadipocytes. In contrast, DHEA stimulated the differentiation of human preadipocytes, which is contrary to its actions in differentiating cultures of preadipocytes from animals.

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Dehydroepiandrosterone-sulfate (DHEAS) reduces adipocyte hyperplasia associated with feeding rats a high-fat diet

Cited by 31 publications

References 0 publications

Endocrine, metabolic and nutritional factors in obesity and their relative significance as studied by factor analysis

Endocrine, metabolic and nutritional factors in obesity and their relative significance as studied by factor analysis

Increased muscular dehydroepiandrosterone levels are associated with improved hyperglycemia in obese rats

Dehydroepiandrosterone alters the growth of stromal vascular cells from human adipose tissue

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