Sex-related differences in the effects of high-fat diets on DHEA-treated rats.

Several studies have investigated the beneficial effects of dehydroepiandrosterone (DHEA) on lipid and glucose metabolism. However, many of these studies are inconclusive about the effects of DHEA administration on metabolic disorders, and there appear to be sex-related differences in the effects of DHEA treatment. Few animal studies have addressed the effects of DHEA on diet-induced metabolic disorders. The present study sought to ascertain whether sex differences exist in the effects of a high-fat diet (HFD) on weight gain, adiposity, and biochemical and hormonal parameters in DHEA-treated rats. Rats were fed a HFD for 4 weeks and simultaneously received treatment with DHEA (10 mg/kg by subcutaneous injection) once weekly. Body weight, retroperitoneal fat depot weight, serum glucose, insulin, and leptin levels, and hepatic lipids were measured. HFD exposure increased the adiposity index in both sexes, the hepatic triglyceride content in both sexes, and the hepatic total cholesterol level in males. Moreover, the HFD induced an increase in blood glucose levels in both sexes, and hyperinsulinemia in males. In this experimental model, DHEA treatment reduced hepatic triglyceride levels only in females, regardless of HFD exposure. Exposure to a HFD, even if it does not cause obesity, may enhance risk factors for metabolic disorders, and males are more sensitive to this effect. DHEA treatment can help prevent metabolic derangements, but its effect varies with sex.

Effects of dehydroepiandrosterone (DHEA) and lactate on glucose uptake in the central nervous system.

Dehydroepiandrosterone (DHEA) prevents brain aging, enhances the cerebral metabolism and interacts with energy substrates. The interaction between lactate and DHEA on glucose uptake and lactate oxidation by various nervous structures was investigated and results demonstrate that the 2-(14)C-deoxiglucose (2-(14)C-Dglucose) uptake was stimulated by 10mM lactate in the hypothalamus and olfactory bulb, inhibited in the cerebral cortex and cerebellum, and unaffected in the hippocampus. We also show that, in both the cerebral cortex and hypothalamus, (14)C-lactate oxidation was higher than (14)C-glucose oxidation (p≤0.001), demonstrating a relevant role for lactate as energy substrate. The interaction of lactate and 10(-8)M DHEA was tested and, although DHEA had no significant effect on uptake in the cerebellum, hippocampus, or hypothalamus, 10(-8)M DHEA increased the 2-(14)C-Dglucose uptake in the cerebral cortex in the presence of lactate (p≤0.001), and in the olfactory bulb in the absence of lactate (p<0.05). However, DHEA had no significant effect on (14)C-lactate oxidation. We suggest that DHEA improves glucose uptake in specific conditions. Thus, DHEA may affect CNS metabolism and interact with lactate, which is the most important neuronal energy substrate, on glucose uptake.

Dehydroepiandrosterone improves hepatic antioxidant reserve and stimulates Akt signaling in young and old rats.

This study examined, in the liver of young and old (3- and 24-month-old, respectively) healthy Wistar rats, the in vivo effect of dehydroepiandrosterone (DHEA) (10mg/kg body weight) administered subcutaneously for 5 weeks. Reduced (GSH) and oxidized (GSSG) glutathione levels, glucose-6-phosphate dehydrogenase (G6PDH), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities, hydrogen peroxide concentration, GST and p-Akt/Akt immunocontent ratio were assessed in hepatic tissue. DHEA treatment significantly increased total glutathione content (17%) and GSH (22%) in 3- and 24-month-old treated groups when compared to control groups. The aging factor increased G6PDH (51%) and GPx (22%) activities as well as the hydrogen peroxide concentration (33%), independently of treatment. DHEA treatment increased p-Akt (54%) and p-Akt/Akt ratio (36%) immunocontents in both treated groups. Increased serum levels of alanine aminotransferase (ALT) in aged rats were reduced by DHEA treatment (34%).

Redox imbalance influence in the myocardial Akt activation in aged rats treated with DHEA.

This study examined, in young and old (3 and 24 month-old, respectively) healthy Wistar rats, the in vivo effect of DHEA (10 mg/kg body weight) administered subcutaneously for 5 weeks. Reduced (GSH) and oxidized (GSSG) glutathione levels, glucose-6-phosphate dehydrogenase (G6PDH), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and thioredoxin (Trx) reductase activities, hydrogen peroxide steady-state concentration and Nrf2, GST, Trx-1, Akt and p-Akt expressions were assessed in heart tissue. DHEA treatment significantly increased GST activity in 3 and 24 month-old treated groups. The aging factor diminished hydrogen peroxide concentration and Nrf2 expression, independently of treatment. However, the aging process increased GST, Akt and p-Akt expressions in both 24 month-old groups. The aged group responded differently to DHEA respective to GSSG content, GPx activity and p-Akt concentration. Further studies are needed to form conclusions about the efficacy and safety of DHEA replacement in the elderly, and to better understand DHEA's net effect on oxidative stress parameters and its modulation of signaling cascades.

DHEA effects on myocardial Akt signaling modulation and oxidative stress changes in aged rats.

The secretion of DHEA-synthesized mainly in the adrenal cortex-increases in the postnatal aging, peaks in the twenties and decreases with age afterwards. Exogenous DHEA can exert a dual effect depending on dose and on tissue. Akt is a serine/threonine kinase whose activity has been seen as an interventional approach for cardiomyopathic damage resulting from aging changes. In order to evaluate DHEA effects over myocardial Akt protein expression associated to oxidative stress markers during aging, male Wistar rats (3 and 18 months) were assigned into two groups: control or DHEA (10mg/kg, subcutaneously, for 5 weeks). In the aged group, we found increased lipid peroxidation and glutathione-S-transferase activity. DHEA produced an increase in p-Akt protein expression and a decrease in SOD activity in both ages. Akt pathway activation might be related to changes in oxidative stress parameters according to age.