Sex differences due to dehydroepiandrosterone (DHEA) feeding affecting dehydroepiandrosterone sulfate secretion in golden Syrian hamsters.

The metabolism of orally administered dehydroepiandrosterone (DHEA) by male and female golden Syrian hamsters was examined by quantification of DHEA and dehydroepiandrosterone sulfate (DHEAS) in gallbladder bile, urine and feces using high-performance liquid chromatography (HPLC). Plasma levels of DHEA and DHEAS were also determined by radioimmunoassay (RIA). After 5 days of oral DHEA administration (100 mg/kg body weight twice a day), RIA showed that plasma levels of DHEA and DHEAS were increased approximately 3-6 and 4-5 times, respectively, compared to controls. More than 95 % of circulating DHEA (S) in the peripheral blood was DHEAS. There was no significant sex difference in DHEAS plasma levels between male and female animals in the DHEA-supplemented group. However, 0.2 - 0.3 % of ingested DHEA was conjugated to DHEAS and excreted in urine by females, whereas less than 0.002 % was excreted in urine by males (p < 0.005). DHEAS was excreted in bile by males after DHEA supplementation, and the sex differences in DHEAS levels observed in bile were statistically significant (male, 18.7 +/- 7.5 vs. female, 5.6 +/- 3.1 micromol/l) (p < 0.005). Small amounts of ingested DHEA were excreted in an unchanged state in feces, and no sex difference was observed. These results suggest that there is a considerable sex difference in the conjugation and excretion of orally administered DHEA in the hamster.     

The young göttingen minipig as a model of childhood and adolescent obesity: Influence of diet and gender

Objective:

Gender and sex hormones influence the development of obesity and metabolic syndrome in humans and Göttingen minipigs. The aim of this study was to investigate possible gender differences in the metabolic response to a high energy diet in young Göttingen minipigs as a model of childhood/adolescent obesity.

Design and Methods:

Nine‐week‐old male and female Göttingen minipigs were fed restrictedly on either a low energy diet (LED) or a high energy diet (HED) for 4 months (n = 5‐7). Parameters of interest were fat percentage, visceral fat mass, plasma lipids and glucose tolerance, insulin resistance, and β‐cell function measured by oral and intravenous glucose tolerance tests.

Results:

At 11 to 12 weeks of age, after 2 weeks diet feeding, both genders on HED had increased fat percentage, glucose intolerance, decreased insulin sensitivity, and increased plasma levels of cholesterol and triglycerides (TGs). There was no gender difference in body weight (BW) or fat percentage, but males had lower glucose tolerance than females. After 3.5 to 4 months on the diets, the pigs on HED had increased BW, fat percentage, and visceral fat mass and were more glucose intolerant and insulin resistant than pigs on LED. Also increases in plasma cholesterol and TG levels were observed in the pigs on HED. Females had higher fat percentage and more visceral fat, were more insulin resistant, and had a more unfavorable lipid profile compared with males independent of diet.

Conclusion:

In conclusion, the young Göttingen minipig, and especially the female gender, seems to be a potential model for diet induced childhood/adolescent obesity and metabolic syndrome.     

Improvements in cardiovascular risk profile with large-volume liposuction: a pilot study

In this study, the authors investigated the physiologic effects of the altered body composition that results from surgical removal of large amounts of subcutaneous adipose tissue. Fourteen women with body mass indexes of greater than > 27 kg/m2 underwent measurements of fasting plasma insulin, triglycerides, cholesterol, body composition by dual-energy x-ray absorptiometry (DXA), resting energy expenditure, and blood pressure before and after undergoing large-volume ultrasound-assisted liposuction.There were no significant intraoperative complications. Body weight had decreased by 5.1 kg (p < 0.0001) by 6 weeks after liposuction, with an additional 1.3-kg weight loss (p < 0.05) observed between 6 weeks and 4 months after surgery, for a total weight loss of 6.5 kg (p < 0.00006). Body mass index decreased from (mean +/- SEM) 28.8 +/- 2.3 to 26.8 +/- 1.5 kg/m2 (p < 0.0001). This change in body weight was primarily the result of decreases in body fat mass: as assessed by DXA, lean body mass did not change (43.8 +/- 3.1 kg to 43.4 +/- 3.6 kg, p = 0.80), whereas DXA total body fat mass decreased from 35.7 +/- 6.3 to 30.1 +/- 6.5 kg (p < 0.0001). There were significant decreases in fasting plasma insulin levels (14.9 +/- 6.5 mIU/ml before liposuction versus 7.2 +/- 3.2 mIU/ml 4 months after liposuction, p < 0.007), and systolic blood pressure (132.1 +/- 7.2 versus 120.5 +/- 7.8 mmHg, p < 0.0002). Total cholesterol, high-density lipoprotein cholesterol, plasma triglycerides, and resting energy expenditure values were not significantly altered after liposuction.In conclusion, over a 4-month period, large-volume liposuction decreased weight, body fat mass, systolic blood pressure, and fasting insulin levels without detrimental effects on lean body mass, bone mass, resting energy expenditure, or lipid profiles. Should these improvements be maintained over time, liposuction may prove to be a valuable tool for reducing the comorbid conditions associated with obesity.     

Territorial aggression and hormones during the non-breeding season in a tropical bird

The hormonal control of territorial aggression in male and female vertebrates outside the breeding season is still unresolved. Most vertebrates have regressed gonads when not breeding and do not secrete high levels of sex steroids. However, recent studies implicate estrogens in the regulation of non-breeding territoriality in some bird species. One possible source of steroids during the non-breeding season could be the adrenal glands that are known to produce sex steroid precursors such as dehydroepiandrosterone (DHEA). We studied tropical, year-round territorial spotted antbirds (Hylophylax n. naevioides) and asked (1). whether both males and females are aggressive in the non-breeding season and (2). whether DHEA is detectable in the plasma at that time. We conducted simulated territorial intrusions (STIs) with live decoys to male and female free-living spotted antbirds in central Panama. Non-breeding males and females displayed robust aggressive responses to STIs, and responded more intensely to decoys of their own sex. In both sexes, plasma DHEA concentrations were detectable and higher than levels of testosterone (T) and 17beta-estradiol (E(2)). In males, plasma DHEA concentrations were positively correlated with STI duration. Next, we conducted STIs in captive non-breeding birds. Captive males and females displayed robust aggressive behavior. Plasma DHEA concentrations were detectable in both sexes, whereas T was non-detectable (E(2) was not measured). Plasma DHEA concentrations of males were positively correlated with aggressive vocalizations and appeared to increase with longer STI durations. We conclude that male and female spotted antbirds can produce DHEA during the non-breeding season and DHEA may serve as a precursor of sex steroids for the regulation of year-round territorial behavior in both sexes.     

Protein and lipid utilization during fasting with shallow and deep hypothermia in the European hedgehog (Erinaceus europaeus)

We investigated whether the relative contributions of body protein and lipid reserves differ according to the level of energy expenditure in fasting animals. Protein and lipid utilization was therefore quantified and compared in hedgehogs which fasted with shallow and deep hypothermia, i.e. by exposure at 5 or 20 °C ambient temperature. Body composition was determined for every 150-g decrease in mass throughout the experiment, allowing the calculation of regression lines between body mass (independent variable, x) and body composition (dependent variable, y: water, protein, neutral lipids, phospholipids and cholesterol). There were highly significant (P<0.001) linear decreases in all body components with decreasing body mass in both groups of hedgehogs. Neutral lipids were the main component of the total body mass loss (54%) in fasted animals with shallow and deep hypothermia, percentages of water (26–30%) and protein (10–11%) being lower, and those of phospholipid and cholesterol negligible (<0.5%). In spite of different levels in energy expenditure (2.54 and 1.07 W·kg^-1 in shallow-and deep-hypothermal fasting hedgehogs, respectively), the energy sources were identical in both groups, neutral lipid being the main fuel (91–92%) and body protein accounting for the remainder (8–9%). Prolonged fasting with shallow and deep hypothermia were marked by low alaninemia and glycemia, while plasma free fatty acids and -hydroxybutyrate were elevated. These data therefore indicate that the relative contribution of lipid and protein is similar during prolonged fasting with shallow and deep hypothermia, i.e. there is no specific effect of deep hypothermia on body fuel utilization. The tolerance of a much longer fast in deep-hypothermal hedgehogs can simply be attributed to the lower rates of lipid and protein utilization as a result of the lower level of energy expenditure.Abbreviations bm body mass     

Significant intramyocellular lipid use during prolonged cycling in endurance-trained males as assessed by three different methodologies

Intramyocellular triacylglycerol (IMTG) has been suggested to represent an important substrate source during exercise. In the present study, IMTG utilization during exercise is assessed through the use of various methodologies. In addition, we identified differences in the use of intramyocellular lipids deposited in the immediate subsarcolemmal (SS) area and those stored in the more central region of the fiber. Contemporary stable isotope technology was applied in combination with muscle tissue sampling before and immediately after 3 h of moderate-intensity cycling exercise (62 +/- 2% Vo(2 max)) in eight well-trained male cyclists. Continuous infusions with [U-13C]palmitate and [6,6-(2)H2]glucose were applied to quantify plasma free fatty acid (FFA) and glucose oxidation rates and to estimate whole body IMTG and glycogen use. Both immunohistochemical analyses of oil red O (ORO)-stained muscle cross sections and biochemical triacylglycerol (TG) extraction were performed to assess muscle lipid content. During exercise, plasma FFA, muscle (and/or lipoprotein)-derived TG, plasma glucose, and muscle glycogen oxidation contributed 24 +/- 2, 22 +/- 3, 11 +/- 1, and 43 +/- 3% to total energy expenditure, respectively. In accordance, a significant net decline in muscle lipid content was observed following exercise as assessed by ORO staining (67 +/- 8%) and biochemical TG extraction (49 +/- 8%), and a positive correlation was observed between methods (r = 0.56; P < 0.05). Lipid depots located in the SS area were utilized to a greater extent than the more centrally located depots. This is the first study to show significant use of IMTG as a substrate source during exercise in healthy males via the concurrent implementation of three major methodologies. In addition, this study shows differences in resting subcellular intramyocellular lipid deposit distribution and in the subsequent net use of these deposits during exercise.     

Opposing actions of dehydroepiandrosterone and corticosterone in rats.

The purpose of this study was to determine the impact of dehydroepiandrosterone (DHEA) and corticosterone (CORT) treatment, using implants as a route of administration, on specific hormones, metabolites, and enzymes involved in energy metabolism. Sixty male Sprague-Dawley rats, 325 g initial weight, were implanted subcutaneously for 3 weeks with time-release pellets containing either DHEA or CORT at doses of 0, 10, 25, 50, or 100 mg in this 2 x 5 factorial experiment. In general, body weights and food intakes decreased as the level of steroid hormones increased. In contrast to DHEA treatment, rats receiving the 50- and 100-mg doses of CORT had lighter thymus glands and spleens and heavier epididymal and retroperitoneal fat pads than their controls. Rats treated with 100 mg of DHEA had lowered serum levels of triglycerides and lipid hydroperoxides whereas rats treated with 100 mg of CORT had higher levels of these blood lipids compared to their respective controls. In contrast to DHEA treatment, there was a dose-dependent increase in liver lipid content and the specific activities of the hepatic lipogenic enzymes glucose-6-phosphate dehydrogenase, malic enzyme, and fatty acid synthase in response to CORT treatment. Rats treated with 100 mg of DHEA had higher serum levels of IGF-1 than control rats. Conversely, rats treated with 100 mg of CORT had lower serum levels of IGF-1 and higher serum levels of testosterone, progesterone, and insulin than their controls. These data demonstrate the lipogenic actions of corticosterone in rats. Conversely, DHEA treatment reduced serum and hepatic lipids. Furthermore, these data suggest that using implants instead of bolus injections of steroids may be a more physiological approach for studying the influence of these steroids on lipid metabolism.     

Nutrition-induced differences in body composition, compensatory growth and endocrine status in growing pigs

In this experiment, we assessed the effect of amino acid (AA) intake restriction in entire male Yorkshire pigs between 15 and 38 kg BW (restriction phase) on BW gain, body composition and plasma levels of blood urea nitrogen (BUN), cortisol, insulin-like growth factor I (IGF-I), growth hormone (GH) and leptin during the subsequent re-alimentation phase. During the restriction phase, 36 pigs were allotted to one of two dietary treatments: adequate AA intake (control) or AA-limiting diets (AA-30%). Thereafter, pigs were fed common non-limiting diets up to 110 kg BW. Throughout the experiment, pigs were scale-fed at 90% of the estimated voluntary daily digestible energy intake. At the end of the restriction phase, pigs on AA-30% had lesser BW gain (650 v. 784 g/day; P < 0.001), loin area (LA; 12.2 v. 14.2 cm2; P < 0.001), BUN (4.6 v. 6.3 mg/dl; P < 0.02), lesser plasma levels of IGF-I (440 v. 640 ng/m; P < 0.001) and cortisol (8.2 v. 19.2 μg/dl; P < 0.001), greater backfat thickness (BF; 7.56 v. 6.56 mm; P < 0.02), and greater plasma levels of leptin (2.7 v. 1.8 ng/ml; P = 0.027) and GH (3.3 v. 2.0 ng/ml; P = 0.05) than pigs on control. During the re-alimentation phase, previously restricted pigs showed full compensatory growth (CG) in terms of BW gain (1170 v. 1077 g/day; P < 0.002), whole-body protein deposition (Pd) (179 v. 163 g/day; P < 0.001) as well as physical and chemical body composition (whole-body lipid to body protein mass ratio, LB/PB; 1.14 v. 1.15; P > 0.10). Besides GH at 45 kg BW (4.2 v. 2.4 ng/ml; P = 0.066), there were no effects of previous AA intake restriction on leptin, IGF-I and BUN during the re-alimentation phase (P > 0.10). Plasma cortisol and IGF-I levels may act as an indicator of AA-induced restriction in Pd in growing pigs. Plasma BUN level does not appear as a sensitive indicator for compensatory Pd. Plasma leptin and GH levels allow for the involvement of the brain in controlling chemical body composition. Full CG was observed during the energy-dependent phase of Pd in growing pigs and might be driven by a target LB/PB, possibly mediated via plasma leptin, IGF-I and GH levels.     

Age‐related effects of DHEA on peripheral markers of oxidative stress

Ageing is an inevitable biological process characterized by a general decline in various physiological functions. DHEA and DHEAS levels are maximal between the second and third life decades, then start to decline 2% per year, leaving a residual of 10–20% of the peak production by the eighth decade. Erythrocytes are exposed to frequent oxidative stress due to the oxygen radicals continuously generated by haemoglobin auto‐oxidation. We investigated DHEA chronic (10 mg/kg, subcutaneously, for 5 weeks) effects over oxidative stress markers in erythrocytes of male Wistar rats of 3, 13 and 18 month‐old. In the 13 month‐old group, we found increased lipid peroxidation (LPO), superoxide dismutase (SOD), glutathione‐S‐transferase and catalase activities when compared to the other age groups. DHEA produced a marked increase in LPO of 13 month‐old group when compared to its control. DHEA exerted this pro‐oxidant effects in all ages studied, especially in age 13 month‐old. It seems that at 13 month‐old there would be an important depletion of some specific anti‐oxidant in order to determine such susceptibility to DHEA effects. Since this approach allows a minimally invasive assessment, it would be useful as a routine method in human clinical studies investigating DHEA effects during the ageing process. Copyright © 2009 John Wiley & Sons, Ltd.     

The Estrogen Antagonist EM‐652 and Dehydroepiandrosterone Prevent Diet‐ and Ovariectomy‐Induced Obesity

Objective: EM‐652 is a pure antiestrogen in human breast and uterine cancer cells that also reduces bone loss and plasma lipid levels in the rat. This study aimed to assess the ability of EM‐652, alone or with dehydroepiandrosterone (DHEA), to prevent obesity and related metabolic abnormalities induced by an obesity‐promoting diet and ovariectomy. Research Methods and Procedures: Female rats were fed a high‐sucrose, high‐fat (HSHF) diet, were left intact or ovariectomized (OVX), and were treated with EM‐652, DHEA, or both for 20 days. Variables of energy balance and determinants of lipid metabolism and insulin sensitivity were assessed. Results: The HSHF diet (vs. chow) and OVX both increased energy intake and gain, as well as energetic efficiency. Both EM‐652 and DHEA prevented diet‐ and OVX‐induced energy gain mainly by decreasing fat deposition, without being additive. The modest EM‐652‐induced increase in liver triglycerides of intact rats was prevented by its combination with DHEA. EM‐652, but not DHEA, decreased cholesterolemia. The HSHF diet and OVX reduced insulin sensitivity, an effect that was attenuated by EM‐652 and abrogated by DHEA and EM‐652+DHEA. Treatment with EM‐652, DHEA, or their combination abolished the diet‐ and OVX‐induced increase in adipose lipoprotein lipase activity that accompanied fat gain. Discussion: EM‐652 is an effective agent to prevent diet‐ and OVX‐induced obesity and its associated cardiovascular risk factors such as insulin resistance. The addition of DHEA prevents hepatic lipid accumulation and further ameliorates insulin sensitivity. The beneficial metabolic effects of such combined steroid therapy may, therefore, eventually prove to be clinically relevant.     

Dietary fat saturation and gender/hormonal status modulate plasma lipids and lipoprotein composition(1)

Male, female and ovariectomized (to mimic menopause) guinea pigs were fed a saturated (SFA) or a polyunsaturated (PUFA) fat diet for 4 weeks to determine the effects of dietary fat saturation on lipoprotein levels and composition and to assess whether gender and hormonal status modulate the cholesterolemic response. Both diets contained 15g/100 g fat and 0.04 g/100 g cholesterol and were identical in composition except for the type of fat. The SFA diet contained 50% saturated fat (25% lauric + myristic fatty acids), 25% PUFA and 25% monounsaturated fatty acids while the PUFA diet had 50% PUFA (linoleic acid), 25% monounsaturated and 25% SFA fatty acids. Plasma LDL cholesterol (LDL-C) was an average 21% lower in guinea pigs fed PUFA compared to those fed SFA (P < 0.05). In addition, ovariectomized guinea pigs, both in the SFA and PUFA groups, had 20–33% higher LDL-C than either males or females (P < 0.01). VLDL cholesterol was 70% higher in the PUFA-fed animals (P < 0.0001). A gender effect was observed in plasma HDL cholesterol (HDL-C) with females and ovariectomized guinea pigs having 30–42% higher HDL-C than males (P < 0.01). LDL susceptibility to oxidation was not affected by dietary fat saturation or gender. In contrast, VLDL and LDL composition were significantly influenced by diet and gender. VLDL particles were larger in size in guinea pigs fed the SFA diets (P < 0.01) while LDL particles were larger in female guinea pigs (P < 0.001). Hepatic lipids were influenced by the interaction between diet and group. Hepatic cholesterol (P < 0.01) and TAG concentrations (P < 0.0001) were highest in female guinea pigs fed the PUFA diet. Since the liver is the major site of lipoprotein synthesis and catabolism, these results suggest that not only diet but also gender may play a major role in determining the composition and size of lipoproteins.     

Sex differences in DHEA and estradiol during development in a wild songbird: Jugular versus brachial plasma

Sexual differentiation of the brain has traditionally been thought to be driven by gonadal hormones, particularly testosterone (T). Recent studies in songbirds and other species have indicated that non-gonadal sex steroids may also be important. For example, dehydroepiandrosterone (DHEA) - a sex steroid precursor that can be synthesized in the adrenal glands and/or brain - can be converted into active sex steroids, such as 17β-estradiol (E₂), within the brain. Here, we examine plasma DHEA and E₂ levels in wild developing European starlings (Sturnus vulgaris), from hatch (P0) to fledging (P20). Blood samples were collected from either the brachial vein (n = 143) or the jugular vein (n = 129). In songbirds, jugular plasma is enriched with neurally-synthesized steroids and, therefore, jugular plasma is an indirect measure of the neural steroidal milieu. Interestingly, brachial DHEA levels were higher in males than females at P4. In contrast, jugular DHEA levels were higher in females than males at P0 and P10. Brachial E₂ levels were higher in males than females at P6. Surprisingly, jugular E₂ levels were not high and showed no sex differences. Also, we calculated the difference between brachial and jugular steroid levels. At several ages, jugular steroid levels were lower than brachial levels, particularly in males, suggesting greater neural metabolism of circulating DHEA and E₂ in males than females. At a few ages, jugular steroid levels were higher than brachial levels, suggesting neural secretion of DHEA or E₂ into the general circulation. Taken together, these data suggest that DHEA may play a role in brain sexual differentiation in songbirds.     

Dehydroepiandrosterone (DHEA) increases territorial song and the size of an associated brain region in a male songbird

In many species, male territorial aggression is tightly coupled with gonadal secretion of testosterone (T). In contrast, in song sparrows (Melospiza melodia morphna), males are highly aggressive during the breeding (spring) and nonbreeding (autumn and early winter) seasons, but not during molt (late summer). In aggressive nonbreeding song sparrows, plasma T levels are basal (< or = 0.10 ng/ml), and castration has no effect on aggression. However, aromatase inhibitors reduce nonbreeding aggression, indicating a role for estrogen in wintering males. In the nonbreeding season, the substrate for brain aromatase is unclear, because plasma T and androstenedione levels are basal. Aromatizable androgen may be derived from plasma dehydroepiandrosterone (DHEA), an androgen precursor. DHEA circulates at elevated levels in wintering males (approximately 0.8 ng/ml) and might be locally converted to T in the brain. Moreover, plasma DHEA is reduced during molt, as is aggression. Here, we experimentally increased DHEA in wild nonbreeding male song sparrows and examined territorial behaviors (e.g., singing) and discrete neural regions controlling the production of song. A physiological dose of DHEA for 15 days increased singing in response to simulated territorial intrusions. In addition, DHEA treatment increased the volume of a telencephalic brain region (the HVc) controlling song, indicating that DHEA can have large-scale neuroanatomical effects in adult animals. The DHEA treatment also caused a slight increase in plasma T. Exogenous DHEA may have been metabolized to sex steroids within the brain to exert these behavioral and neural effects, and it is also possible that peripheral metabolism contributed to these effects. These are the first results to suggest that exogenous DHEA increases male-male aggression and the size of an entire brain region in adults. The data are consistent with the hypothesis that DHEA regulates territorial behavior, especially in the nonbreeding season, when plasma T is basal.     

Aerobic power and insulin action improve in response to endurance exercise training in healthy 77-87 yr olds.

Previous studies have demonstrated that frail octogenarians have an attenuated capacity for cardiovascular adaptations to endurance exercise training. In the present study, we determined the magnitude of cardiovascular and metabolic adaptations to high-intensity endurance exercise training in healthy, nonfrail elderly subjects. Ten subjects [8 men, 2 women, 80.3 yr (SD2.5)] completed 10-12 mo (108 exercise sessions) of a supervised endurance exercise training program consisting of 2.5 sessions/wk (SD 0.2), 58 min/session (SD 6), at an intensity of 83% (SD 5) of peak heart rate. Primary outcomes were maximal attainable aerobic power [peak aerobic capacity (Vo(2peak))]; serum lipids, oral glucose tolerance, and insulin action during a hyperglycemic clamp; body composition by dual-energy X-ray absorptiometry, and energy expenditure using doubly labeled water and indirect calorimetry. The training program resulted in an increase in Vo(2peak) of 15% (SD 7) [22.9 (SD 3.3) to 26.2 ml.kg(-1).min(-1) (SD 4.0); P < 0.0001]. Favorable lipid changes included reductions in total cholesterol (-8%; P = 0.002) and LDL cholesterol (-10%; P = 0.003), with no significant change in HDL cholesterol or triglycerides. Insulin action improved, as evidenced by a 29% increase in glucose disposal rate relative to insulin concentration during the hyperglycemic clamp. Fat mass decreased by 1.8 kg (SD 1.4) (P = 0.003); lean mass did not change. Total energy expenditure increased by 400 kcal/day because of an increase in physical activity. No change occurred in resting metabolism. In summary, healthy nonfrail octogenarians can adapt to high-intensity endurance exercise training with improvements in aerobic power, insulin action, and serum lipid and lipoprotein risk factors for coronary heart disease; however, the adaptations in aerobic power and insulin action are attenuated compared with middle-aged individuals.     

Increase in plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide as a marker of peripheral androgen action in hirsutism: a side-effect induced by cyclosporine A

Dose-dependent hypertrichosis is a common dermatological side-effect affecting the majority of patients treated with cyclosporine A (CSA). Previous studies have not demonstrated the influence of CSA on specific sex hormone levels. The aim of this study is to investigate whether CSA increases the activity of 5 alpha-reductase, an enzyme which transforms androgens into dihydrotestosterone in peripheral tissues. The metabolite which best reflects this activity is 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (Adiol G). The study was carried out on 49 insulin-dependent diabetes patients participating in the double-blind "Cyclosporine-Diabète-France" clinical trial, of which 28 were treated with CSA (16 males and 12 females), and 21 received only placebo (10 males and 11 females). All patients underwent extensive clinical and laboratory evaluations prior to and during the present study. In addition to Adiol G, testosterone (T), dehydroepiandrosterone sulfate (DHEA S) and sex hormone-binding globulin (SHBG) were assayed. Levels of Adiol G increased significantly in CSA-treated groups: males, 11.86 +/- 2.58 vs 7.83 +/- 2.30 nmol/l; females, 4.48 +/- 2.70 vs 2.10 +/- 1.22 nmol/l; P less than 0.02 (comparison of means). There were no significant differences in this parameter before and during treatment in either the male or female placebo groups (paired t-test). During the treatment period, T, DHEA S, SHBG and the T/SHBG ratio did not significantly change with respect to their baseline values in any of the groups studied (comparison of means). Comparison (using paired t-test) showed a significant increase of DHEA S in CSA-treated groups: males, delta = 3.08 +/- 3.33 nmol/l, P less than 0.01; females, delta = 0.98 +/- 1.13 nmol/l, P less than 0.05. In conclusion, it is possible that CSA induces hypertrichosis or hirsutism by increasing 5 alpha-reductase activity in peripheral tissues. Nevertheless the role of increased DHEA S as a possible Adiol G precursor cannot be excluded.     

Appetite and endocrine regulators of energy balance after 2 days of energy restriction: insulin, leptin, ghrelin, and DHEA-S

Using a double‐blind, placebo‐controlled crossover design, the effects of 48 h near complete energy restriction on endocrine regulators of appetite and satiety were assessed. Twelve men and one woman participated in this controlled, 2‐day diet intervention study. One experimental trial was completed in a calorie deprived state (CAL‐DEP; <10% of estimated energy requirements) and others in a fed condition (carbohydrate only and carbohydrate and fat; data were pooled and compared to CAL‐DEP). Test meals containing prescribed energy intake and indistinguishable in sensory characteristics were provided during each trial. Glucose, insulin, leptin, ghrelin, cortisol, dehydroepiandrosterone‐sulfate (DHEA‐S), and satiety were repeatedly assessed. Mean glucose, insulin, and leptin concentrations were lower (P < 0.0001) for CAL‐DEP compared to the fully fed (FED) state. Ghrelin and DHEA‐S were higher (P < 0.0001) for CAL‐DEP relative to FED. Cortisol levels declined each day regardless of diet (P < 0.0001) but were 32% higher (P < 0.01) at the conclusion of the session for CAL‐DEP compared to FED. Satiety was 25% lower (P < 0.0001) for CAL‐DEP relative to FED and decreased (P < 0.0001) over time regardless of diet. In the FED state, insulin (r = 0.55), glucose (r = 0.76), cortisol (r = ?0.59), and DHEA‐S (r = ?0.62) were associated (P < 0.05) with satiety, but not during CAL‐DEP. These findings show that 2 days of severe energy restriction alter several endocrine regulators of appetite independent of perception of increased hunger suggesting a physiological mechanism to explain overeating following acute periods of severe energy restriction.     

Soluble Fermentable Dietary Fibre (Pectin) Decreases Caloric Intake,Adiposity and Lipidaemia in High-Fat Diet-Induced Obese Rats

Consumption of a high fat diet promotes obesity and poor metabolic health, both of which may be improved by decreasing caloric intake. Satiety-inducing ingredients such as dietary fibre may be beneficial and this study investigates in diet-induced obese (DIO) rats the effects of high or low fat diet with or without soluble fermentable fibre (pectin). In two independently replicated experiments, young adult male DIO rats that had been reared on high fat diet (HF; 45% energy from fat) were given HF, low fat diet (LF; 10% energy from fat), HF with 10% w/w pectin (HF+P), or LF with 10% w/w pectin (LF+P) ad libitum for 4 weeks (n = 8/group/experiment). Food intake, body weight, body composition (by magnetic resonance imaging), plasma hormones, and plasma and liver lipid concentrations were measured. Caloric intake and body weight gain were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Body fat mass increased in HF, was maintained in LF, but decreased significantly in LF+P and HF+P groups. Final plasma leptin, insulin, total cholesterol and triglycerides were lower, and plasma satiety hormone PYY concentrations were higher, in LF+P and HF+P than in LF and HF groups, respectively. Total fat and triglyceride concentrations in liver were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Therefore, the inclusion of soluble fibre in a high fat (or low fat) diet promoted increased satiety and decreased caloric intake, weight gain, adiposity, lipidaemia, leptinaemia and insulinaemia. These data support the potential of fermentable dietary fibre for weight loss and improving metabolic health in obesity.     

DHEA and estradiol levels in brain,gonads, adrenal glands,and plasma of developing male and female European starlings

Traditionally, sexual differentiation of the brain was thought to be driven by gonadal hormones, particularly testosterone (T). However, recent studies in songbirds suggest that other steroids may also be important. For example, dehydroepiandrosterone (DHEA) can be synthesized by the gonads, adrenal glands, and/or brain and locally metabolized into T and 17β-estradiol (E₂). Here, we examined DHEA and E₂ levels in the brain, peripheral tissues, and plasma of wild European starlings (Sturnus vulgaris). In Study 1, samples were collected from males and females at P0 (day of hatch), P6, and P8. In Study 2, samples were collected at P4. At P0, DHEA levels in the diencephalon were higher in males than females. DHEA levels were generally high in the gonads and adrenals, and they were higher in testes than ovaries at P8. Further, E₂ levels were non-detectable in most brain samples, suggesting that DHEA was not metabolized to E₂ or that locally produced E₂ was rapidly inactivated. At P4, DHEA levels in telencephalic regions were lower in males than females. Taken together, these data suggest that sex differences in peripheral DHEA secretion and neural DHEA metabolism at specific ages during development might play a role in sexual differentiation of the songbird brain.     

Energy expenditure and testosterone in free-living male yellow-pine chipmunks

The onset of mating in yellow-pine chipmunks (Tamias amoenus) follows emergence from a prolonged period of energy conservation during hibernation. Energy expenditures are greatly accelerated to meet the demands of the reproductive season. When emerging from hibernation, typical male chipmunks (breeders) have enlarged testes and a high level of plasma testosterone (T). However, certain males that do not participate in reproduction (nonbreeders) maintain small testes and low plasma T levels and emerge several weeks later than the breeders. The timing of the terminal arousal from hibernation and onset of mating are associated with increased plasma T levels. Experimental elevation of T levels in T. amoenus outside the mating season has been associated with a decrease in body mass, further suggesting an effect of T on energy balance. To test this hypothesis, we measured daily energy expenditure (DEE) in free-living, nonbreeding male chipmunks in the presence and absence of a T-implant. We also measured DEE in breeding males when endogenous T levels were high. DEE of the nonbreeders was not affected by our manipulation of plasma T, and the DEE of breeding males did not differ from that of nonbreeders. We conclude that energy expenditure on a daily basis in male yellow-pine chipmunks is not influenced by levels of T. However, on a seasonal basis, the earlier emergence from hibernation by breeding males, which appears to be influenced by T, represents an overall seasonal energy expenditure that exceeds that of nonbreeding males.     

Effects of fermentable starch and straw-enriched housing on energy partitioning of growing pigs

Both dietary fermentable carbohydrates and the availability of straw bedding potentially affect activity patterns and energy utilisation in pigs. The present study aimed to investigate the combined effects of straw bedding and fermentable carbohydrates (native potato starch) on energy partitioning in growing pigs. In a 2 × 2 factorial arrangement, 16 groups of 12 pigs (approximately 25 kg) were assigned to either barren housing or housing on straw bedding, and to native or pregelatinised potato starch included in the diet. Pigs were fed at approximately 2.5 times maintenance. Nitrogen and energy balances were measured per group during a 7-day experimental period, which was preceded by a 30-day adaptation period. Heat production and physical activity were measured during 9-min intervals. The availability of straw bedding increased both metabolisable energy (ME) intake and total heat production (P < 0.001). Housing conditions did not affect total energy retention, but pigs on straw bedding retained more energy as protein (P < 0.01) and less as fat (P < 0.05) than barren-housed pigs. Average daily gain (P < 0.001), ME intake (P < 0.001) and energy retention (P < 0.01) were lower in pigs on the native potato starch diet compared to those on the pregelatinised potato starch diet. Pigs on the pregelatinised potato starch diet showed larger fluctuations in heat production and respiration quotient over the 24-h cycle than pigs on the native potato starch diet, and a higher activity-related energy expenditure. The effect of dietary starch type on activity-related heat production depended, however, on housing type (P < 0.05). In barren housing, activity-related heat production was less affected by starch type (16.1% and 13.7% of total heat production on the pregelatinised and native potato starch diet, respectively) than in straw-enriched housing (21.1% and 15.0% of the total heat production on the pregelatinised and native potato starch diet, respectively). In conclusion, the present study shows that the availability both of straw bedding and of dietary starch type, fermentable or digestible, affects energy utilisation and physical activity of pigs. The effects of housing condition on protein and fat deposition suggest that environmental enrichment with long straw may result in leaner pigs. The lower energy expenditure on the physical activity of pigs on the native potato starch diet, which was the most obvious in straw-housed pigs, likely reflects a decrease in foraging behaviour related to a more gradual supply of energy from fermentation processes.