[show abstract][hide abstract] ABSTRACT: Morphometric and hormonal measures were collected from 21 captive savanna baboons (Papio cynocephalus) maintained at the Tulane National Primate Research Center in order to determine age-related patterns in leptin levels over the life course as well as their relationships to body composition and adrenal and gonadal steroids. Comparison of leptin levels between peri-pubertal, adolescent, young adult, and fully mature males show lower levels among adolescent as compared with young adult males (P = 0.05 by Kruskal-Wallis ANOVA). In addition, abdominal fat varied among age groups (P = 0.003 by Kruskal-Wallis ANOVA) with the peri-pubertal animals lower than the adolescents, young adults, and prime adults. However leptin was not related to any measure of body composition, including abdominal fat, or to adrenal hormones (dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol) or gonadal hormones (testosterone and estradiol). Age-related changes in leptin appear similar to those reported for captive rhesus macaques, while the failure to find an association between leptin and abdominal fat is interestingly different. These results confirm elevated levels of leptin in captive baboons compared with their wild counterparts and suggest that they result from changes in fetal development.
Journal of Medical Primatology 01/2004; 32(6):320-4. · 1.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Morphometric and hormonal measures were collected from 21 captive savanna baboons (Papio cynocephalus) maintained at the Tulane National Primate Research Center in order to determine age-related patterns in leptin levels over the life course as well as their relationships to body composition and adrenal and gonadal steroids. Comparison of leptin levels between peri-pubertal, adolescent, young adult, and fully mature males show lower levels among adolescent as compared with young adult males (P = 0.05 by Kruskal–Wallis ANOVA). In addition, abdominal fat varied among age groups (P = 0.003 by Kruskal–Wallis ANOVA) with the peri-pubertal animals lower than the adolescents, young adults, and prime adults. However leptin was not related to any measure of body composition, including abdominal fat, or to adrenal hormones (dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol) or gonadal hormones (testosterone and estradiol). Age-related changes in leptin appear similar to those reported for captive rhesus macaques, while the failure to find an association between leptin and abdominal fat is interestingly different. These results confirm elevated levels of leptin in captive baboons compared with their wild counterparts and suggest that they result from changes in fetal development.
Journal of Medical Primatology 11/2003; 32(6):320 - 324. · 1.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Treatments of human and rodent obesity frequently involve administration of amphetamine derivatives, much like phenylpropanolamine, which suppress food intake. The Zucker rat is a commonly employed model of youth-onset obesity in which the homozygous genotype manifests hyperphagia as well as other characteristics that parallel human obesity. Using a macronutrient selection procedure, we examined phenylpropanolamine's differential actions in controlling dietary intake, spontaneous open-field activity, and regional hypothalamic neurotransmitter levels in obese female Zucker rats of varying fat food preference. We hypothesized that phenylpropanolamine would alter hypothalamic monoamine levels differently in low-fat preferring and high-fat preferring Zucker rats, and hence affect feeding behavior and activity differently in these two groups. It was found that in high-fat preferring animals, phenylpropanolamine significantly decreased spontaneous open-field activity, decreased only carbohydrate caloric intake, and increased serotonin and 5-HIAA levels in the paraventricular nucleus (PVN). In low-fat preferring animals, phenylpropanolamine decreased carbohydrate, protein, and total caloric intake, had no significant effect of spontaneous activity, and increased serotonin and 5-hydroxyindole acetic acid levels in the PVN. Inherent and induced physiological differences of low-fat and high-fat preferring animals are discussed as well as phenylpropanolamine's potential in combination drug therapy for the treatment of human hyperphagic obesity.
[show abstract][hide abstract] ABSTRACT: Insulin-resistant muscle tissue contains low proportions of arachidonic acid (AA), and increased proportions of muscle AA correlate with improved insulin sensitivity. Dehydroepiandrosterone (DHEA) and AA, like the thiazolidinedione drugs that decrease insulin resistance (IR), are peroxisome proliferators. Long-chain fatty acids (FA) have been named the "one true" endogenous ligand for activating the peroxisome proliferator-activator receptor (PPAR), and DHEA has been named a "good candidate" as a naturally occurring indirect activator of PPAR. This study was conducted to determine DHEA's effects on lipid profiles of skeletal and cardiac muscle in lean and obese Zucker rats (ZR), a model of IR, type 2 diabetes mellitus, and obesity. We hypothesize that DHEA may alter long-chain FA profiles in muscle tissue of obese rats such that they more closely resemble that of the lean. In our experiments, we employed a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. For 30 d, the diet of the two DHEA groups was supplemented with 0.6% DHEA; PF groups were given the average daily calories consumed by their corresponding treatment group. Hearts and gastrocnemius muscles were assayed for phospholipid (PL), free FA, and triglyceride (TG) FA profiles. The proportion of PL AA was significantly greater in both muscle types of lean compared to obese rats. Hearts from both DHEA groups had greater PL proportions of AA and less oleic (18:1) acid than their PF controls. Likewise, 18:1 proportions were significantly lower in the gastrocnemius; however, AA proportions were not significantly different. Similar phenotypic profile differences were observed in the TG fraction of both muscle types. There were no DHEA-related TG FA profile alterations.
[show abstract][hide abstract] ABSTRACT: Though baboons have been considered an appropriate non-human primate model for studying human reproductive and endocrine development. the overall similarity of reproductive maturation between the two species is unclear. This paper examines the role of testicular and adrenal hormones for pubertal changes in a cross-sectional sample of 21 captive male savanna baboons. Morphometric and hormonal indices demonstrate changes in size and gonadal function, but not adrenal function, during pubertal maturation among baboons. Results also indicate that gonadal, but not adrenal, androgens are related to morphometric variables. We conclude that savanna baboons do not make an appropriate evolutionary model of human pubertal maturation.
Journal of Medical Primatology 11/2001; 30(5):273-82. · 1.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Elevated levels of serum free fatty acids (FFA) may be the metabolic alteration in obesity that leads to insulin resistance (IR) and type 2 diabetes mellitus (DM). The obese Zucker rat (ZR) is a genetic model of juvenile-onset obesity and type 2 DM. Compared with its lean sibling, the obese ZR is hyperinsulinemic, hypertriglyceridemic, and, beginning at about 6 months, hyperglycemic. The obese ZR demonstrates also IR, hyperphagia, increased lipogenesis, adipocyte hypertrophy and hyperplasia, and increased serum FFA levels. This study was designed to determine if serum FFA levels in lean and obese ZRs correlate with metabolic parameters associated with altered energy metabolism and IR. We hypothesized that serum FFA levels correlate with such serum parameters such as insulin, glucose, triglyceride, and total cholesterol, as well as such tissue parameters as retroperitoneal, perirenal, and epididymal fat pad weights and liver total lipid content. Twenty lean and 20 obese ZR were age/weight matched. For 14 days each rat had ad libitum access to a single bowl diet that was 50% fat, 30% carbohydrate, and 20% protein. Body weights and caloric intakes were measured daily. After 14 days, all animals were fasted overnight and euthanized. Serum and tissue measurements were made and various parameters were correlated with FFA levels. Serum FFA levels were almost 2 times higher in the obese ZR (approximately 1 mmol/L) compared to the lean (approximately 0.6 mmol/L). Each variable measured was significantly (p < or = 0.05) greater in the obese ZR compared to the lean. There were significant correlations between serum FFA levels and certain variables when data from all ZR were plotted against serum and tissue parameters. However, within phenotypes, there were no significant correlations. Serum FFA levels predict serum and tissue parameters that accompany obesity and IR when comparing lean and obese rats. However, FFA do not predict such parameters within one phenotype.
Life Sciences 10/2001; 69(22):2675-83. · 2.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: High levels of serum free fatty acids (FFA) and lower proportions of polyunsaturated (PU) FAs, specifically arachidonic acid (AA), are common in obesity, insulin resistance (IR), and type 2 diabetes mellitus. Dehydrepiandrosterone (DHEA) decreases body fat content, dietary fat consumption, and insulin levels in obese Zucker rats (ZR), a genetic model of human youth onset obesity and type 2 diabetes. This study was conducted to investigate DHEA's effects on lean and obese ZR serum FFA levels and total lipid (TL) FA profiles in heart and soleus muscle. We postulated that DHEA alters serum FFA levels and tissue TL FA profiles of obese ZR so that they resemble the levels and profiles of lean ZR. If so, DHEA may directly or indirectly alter tissue lipids, FFA flux, and perhaps lower IR in obese ZR. Lean and obese male ZR were divided into six groups with 10 animals in each: obese ad libitum control, obese pair-fed, obese DHEA, lean ad libitum control, lean pair-fed, and lean DHEA. All animals had ad libitum access to a diet whose calories were 50% fat, 30% carbohydrate, and 20% protein. Only the diets of the DHEA treatment groups were supplemented with 0.6% DHEA. Pair-fed groups were given the average number of calories per day consumed by their corresponding DHEA group, and ad libitum groups had 24-h access to the DHEA-free diet. Serum FFA levels and heart and soleus TL FA profiles were measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared to lean (approximately 0.6 mmol/L) ZR, regardless of group. In hearts, monounsaturated (MU) FA were greater and PU FA were proportionally lower in obese compared to the lean rats. In soleus, saturated and MU FA were greater and PU FA were proportionally lower in the obese compared to the lean rats. DHEA groups displayed significantly increased proportions of TL AA and decreased oleic acid in both muscle types. Mechanisms by which DHEA alters TL FA profiles are a reflection of changes occurring within specific lipid fractions such as FFA, phospholipid, and triglyceride. This study provides initial insights into DHEA's lipid altering effects.
Experimental Biology and Medicine 10/2001; 226(8):782-9. · 2.80 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cyclo (His-Pro) (CHP) is a gut-brain peptide whose plasma levels in humans are increased after glucose ingestion and preferentially altered by oral glucose ingestion compared to intravenous administration in rats, suggesting a role in the enteroinsular response to nutrient ingestion. We were interested in examining levels of CHP in women of differing weights and comparing these levels to various parameters of insulin secretion. Plasma from 26 fasting, nondiabetic women ranging from 21 to 70 years of age and weighing 43 to 114 kg was assayed for CHP. Insulin and C-peptide levels were measured in 17 of the 26. Fasting CHP levels were elevated in obese compared to nonobese women (2075+/-144 vs. 905+/-187 pg/ml; p < 0.001) and were related by regression analysis to weight (r = 0.668, p < 0.001) and body mass index (r = 0.636, p = 0.001). The fasting C peptide/insulin molar ratio, which may be used as an estimate of hepatic insulin clearance (HIC), was inversely related to CHP levels (r = -0.568, p = 0.017). We conclude CHP levels are increased in obese women and inversely related to their C-peptide/insulin molar ratio. The elevation of CHP in those with a decrease in this estimate of HIC (obese) is interesting as the greater insulin response seen in normal persons after oral glucose compared to intravenous glucose has been postulated to be due to a decrease in HIC by some gut factor. The presence of such a factor in excess in the obese might explain part of their hyperinsulinemia.
[show abstract][hide abstract] ABSTRACT: The obese Zucker rat exhibits insulin resistance, develops nephropathy at an early age, and may be a model of diabetic nephropathy. Dehydroepiandrosterone (DHEA) may ameliorate many of the factors that contribute to diabetic nephropathy, while angiotensin-converting enzyme inhibitors are known to be effective. One marker of nephropathy is the expression of alpha-smooth muscle actin.
We studied the effect of DHEA on the expression of alpha-smooth muscle actin in obese Zucker rats and compared the changes with those in a control group, a group given quinapril, and a group on a low-calorie diet. DHEA (0.6%) added to plain chow, quinapril (0.3 mg/kg) added to drinking water, and a low-calorie diet based on pair-feeding were administered to obese rats from age 4 to 20 weeks. Immunohistochemical expression of alpha-smooth muscle actin, a marker of interstitial and glomerular fibrosis and an early indicator of nephropathy, was measured semiquantitatively in glomeruli, cortical interstitium, and medullary interstitium on a scale of 0 to 4 and was reported as mean +/- SEM.
When compared with the obese control group, quinapril exhibited a marked reduction in alpha-smooth muscle actin staining in glomeruli, cortical interstitium, and medullary interstitium (P < 0.0005); DHEA reduced alpha-smooth muscle actin staining in cortical interstitium and medullary interstitium (P < 0. 005), and a low-calorie diet reduced alpha-smooth muscle actin staining in cortical and medullary interstitium (P < 0.005), which was similar to the effects of DHEA.
DHEA was similar to a low-calorie diet in reducing the immunohistochemical staining of alpha-smooth muscle actin in obese Zucker rats. However, quinapril exerted a marked protective effect on the development of fibrosis, as indicated by alpha-smooth muscle actin staining, which was significantly less than that of DHEA at the doses studied.
Kidney International 02/2001; 59(1):37-43. · 7.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Abnormalities of the production of dehydroepiandrosterone (DHEA), the adrenal androgen, have been linked with disorders such as obesity and psychological disorders such as major depression. Adrenocorticotropin (ACTH) is the primary stimulant of DHEA, and cortisol, from the adrenal. We chose to examine the DHEA and DHEA/cortisol response to the novel low-dose ACTH test in healthy subjects and a cohort with chronic fatigue syndrome (CFS): this test is useful in assessing subtle irregularities of pituitary-adrenal activity. Nineteen CFS subjects (diagnosed by CDC criteria) and 10 healthy subjects were examined. We demonstrated that 1 microg ACTH significantly elevates DHEA levels, with no difference in output between CFS and healthy subjects. The DHEA/cortisol ratio decreased in response to ACTH stimulation in healthy subjects but not in the CFS cohort. We suggest this divergence of response between the two groups represents an imbalance in the relative synthetic pathways of the CFS group which, if present chronically and if comparable to daily stressors, may manifest itself as an inappropriate response to stress. This difference may be important in either the genesis or propagation of the syndrome.
Psychiatry Research 01/2001; 97(1):21-8. · 2.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: When allowed to select between macronutrients in a 1-h-a-day meal paradigm, Zucker rats consume 20-80% of their total caloric intake as fat. If they receive an intraperitoneal injection of DHEA 2 h before such a test meal, they consume fewer total calories. The magnitude of this effect on each macronutrient depends upon the animal's initial preference for fat; the higher the initial fat preference, the more profound is the decrease in caloric intake and the more pronounced the effect on fat consumption. Doses as low as 25 mg DHEA/kg body weight are effective. Lean Zucker rats that prefer to consume a high-fat diet have higher epinephrine and dopamine levels in select regions of the hypothalamus known to control food intake. Administration of DHEA to such animals 2 h before decapitation reduces the content of norepinephrine and these monoamines to levels that mimic the values found in the low-fat-preferring animals. It is hypothesized that exogenous DHEA causes the acute release of norepinephrine, epinephrine, and dopamine in select regions of the hypothalamus, and this release causes a decrease in food intake, particularly fat.
[show abstract][hide abstract] ABSTRACT: High free fatty acid (FFA) levels are common in obesity and in diseases such as diabetes that are associated with the obese state. Dehydroepiandrosterone (DHEA) decreases dietary fat consumption, body fat content, and insulin levels in the obese Zucker rat (ZR), a genetic model of human youth-onset obesity and type 2 diabetes mellitus. This study was conducted to investigate the effects of DHEA on lean and obese ZR serum, adipose, and hepatic tissue fatty acid (FA) profiles and serum FFA levels. Because DHEA is known to decrease fat consumption and body fat, we postulate that DHEA may also alter FA profiles and FFA levels of the obese ZR such that they more closely resemble the profiles and levels of their lean siblings. In this study there was a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. The diet of the treatment groups was supplemented with 0.6% DHEA, and PF groups were given the same average calories consumed by their corresponding DHEA group for 30 d. Fasted animals were sacrificed, and FA profiles and FFA levels were measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared to lean rats (approximately 0.6 mmol/L). After 30 d of DHEA treatment, FFA levels were lower (P < 0.05) in both lean and obese groups. Although several significant differences in FA profile of serum, hepatic, and adipose lipid components were observed between lean and obese ZR, DHEA-related changes were only observed in the serum phospholipid (PL) and liver PL and triglyceride fractions. The slight but significant decrease in serum FFA levels may be reflected by changes in serum PL FA profiles. Specific hepatic FA profile alterations may be related to DHEA's known effects in inducing hepatic peroxisomes. We speculate that such FA changes may give insight into a mechanism for the action of DHEA.
[show abstract][hide abstract] ABSTRACT: The obese Zucker rat has a genetically flawed leptin system and is a model of hyperphagia, obesity, hyperlipidemia, and markedly elevated leptin levels. Dehydroepiandrosterone (DHEA) administration reduces hyperphagia, hyperlipidemia, and obesity in Zucker rats. Since serum leptin levels are associated with body fat, we wondered what the effects of fat pad weight reduction from DHEA administration would have on leptin levels. This experiment investigated the effects of DHEA on intra-abdominal fat pads, serum lipids, and peripheral leptin in male lean and obese Zucker rats that were administered DHEA in their food from 4 weeks of age to 20 weeks. Lean and obese rats received plain chow or chow containing DHEA. Additional chow-fed groups of lean and obese weight-matched controls and obese pair-fed rats helped to control for the reduced body weight, food intake, and fat pad weights seen with DHEA administration. DHEA administration to lean Zucker rats reduced body weight and fat pad weights, but leptin levels showed a lower trend. Among obese rats, both DHEA treatment and pair-feeding reduced body weight and fat pad weights, but only DHEA lowered leptin levels. The weight-matched controls had reductions in fat pad weights similar to the DHEA-treated group, but with increased leptin levels. Thus, DHEA may exert a small, independent effect on leptin levels in this animal model, but the reduction is less than what would be expected.
Proceedings of The Society for Experimental Biology and Medicine 04/2000; 223(3):258-62.
[show abstract][hide abstract] ABSTRACT: To understand the mechanism(s) of appetite modulation by DHEA, we have undertaken a series of studies to examine the effects of DHEA on neurotransmitters and neuropeptides known to affect appetitive behavior. Here, we report the effect of DHEA on serum enterostatin-VPDPR or E, a pentapeptide known to cause selective diminution in fat intake. Four-week-old lean (fa/+) and obese (fa/fa) Zucker rats were divided into control and treatment groups. DHEA-treated groups received powdered chow containing 0.6% DHEA ad lib for 16 weeks. Another group of obese rats was pair fed to match the intake of the obese DHEA-treated rats. At the end of this period, trunk blood was collected from fasted rats for assay of E-like immunoreactivity (E-LI) by ELISA. DHEA treatment caused a significant diminution in circulating E-LI in both lean (control: 2030 +/- 226; treated: 752 +/- 145 ng/mL; n = 10, p < 0.0001) and obese (control: 2489 +/- 391, n = 6; treated: 1123 +/- 185 ng/mL, n = 7; p = 0.0003) rats. Because DHEA treatment decreases caloric intake and body weight, we examined the effect of caloric intake and body weight on E-LI levels. Serum ELI levels were lower in the obese DHEA-treated group compared to that of obese pair fed (pair fed: 1589 +/- 313, n = 6; DHEA: 1123 +/- 185 ng/mL, n = 7), but the differences were statistically insignificant (p = 0.185). Also, both weight-matched lean and obese control rats had significantly (p < 0.008) higher E-LI than their DHEA-treated counterparts. To examine whether the decrease in serum E-LI following DHEA treatment could be due to increased peptide metabolism, the rate of disappearance of endogenous E-LI from serum (obese control and DHEA-treated) at 37 degrees C was evaluated. The results show an attenuation of peptide metabolism in serum from DHEA-treated rats, a finding contrary to our expectations. In summary, DHEA treatment lowers serum E-LI levels both in lean and obese Zucker rats. This decrement in peptide level is not secondary to changes in body weight or caloric intake due to DHEA, or due to altered serum peptide metabolism. Although DHEA appears to be a potent modulator of E-LI levels, the relationship between DHEA and E-LI in relation to appetitive behavior remains to be clarified.
[show abstract][hide abstract] ABSTRACT: The behavioral endpoint of open-field spontaneous activity was used to characterize further the central nervous system actions of dehydroepiandrosterone. DHEA, administered by intraperitoneal injection, causes a dose-dependent decrease in the spontaneous activity of lean and obese Zucker rats when exposed to a novel environment. The midpoint of DHEA's effect is around 50 mg/kg, a dose similar to that which reduces caloric intake of the rat by nearly 50%. d-Fenfluramine, a known anorectic agent, decreases spontaneous activity under the same conditions. Administration of either DHEA or d-fenfluramine leads to changes in serotonin or its metabolite, 5-hydroxyindole acetic acid, in select regions of the brain. These results emphasize that DHEA given peripherally can affect both the level of neurotransimitters and central nervous system function.
[show abstract][hide abstract] ABSTRACT: Studies from both experimental animals and humans suggest that administration of exogenous DHEA may have beneficial endocrine-metabolic, immunologic and neurologic effects. Several groups have administered DHEA to humans, but to the best of our knowledge, no one at this point has published a summary of the relationship between the administered dose of DHEA and the serum levels of steroids attained.
We summarize the relationship between the administered dose of DHEA and the resulting serum level of DHEA and DHEA-S, in humans, from 18 published articles.
Serum levels of DHEA and DHEA-S increase with increasing doses. Doses above 50 mg/day result in levels that are at or above the upper limit of normal for healthy young adults. At doses above 300 mg/day the increment of serum DHEA and DHEA-S appears to reach a plateau.
Those wanting to use supplemental DHEA might consider that doses of 300 mg/day are maximal; they clearly result in supraphysiologic concentrations and above this level doses may have increased side effects without significantly increasing the effective level of serum hormone.
[show abstract][hide abstract] ABSTRACT: Fasted obese, female Zucker rats accustomed to eating a single high fat meal within 1 h a day were treated with intraperitoneal injections of dehydroepiandrosterone (DHEA) and dextrofenfluramine (d-fen), either individually or in combination. Caloric intake was measured over a 1-h period 2 h after drug administration, and results compared to that of vehicle-treated controls. At 50 mg/kg body weight, DHEA did not affect food intake. At doses of < or = 2 mg/kg d-fen did not affect food intake. Together, however, DHEA 50 mg/kg and d-fen < or = 2 mg/kg significantly decreased food intake. At doses of > or = 3 mg/kg d-fen diminished caloric intake by itself, and the addition of DHEA significantly augmented this effect. Neurotransmitter levels in select regions of the hypothalamus of animals treated using a similar drug protocol showed several changes in the levels of serotonin and its metabolite 5 hydroxyindole acetic acid (5-HIAA). It is hypothesized that DHEA augments the production of serotonin while d-fenfluramine enhances its release, and together these two actions may account for the synergistic action of DHEA and d-fenfluramine.
[show abstract][hide abstract] ABSTRACT: The effects of dehydroepiandrosterone (DHEA) on appetite and weight in the Zucker rat have been examined by many investigators who have reported appetite suppression and metabolic effects. However, these studies compared the treated animals to controls of a similar age. Since animals of different sizes consume different amounts of food, perhaps the treated animals should be compared to controls of a similar size. We studied the effects of DHEA on energy intake and weight gain and analysed the effects by age and metabolic body size.
Lean (n = 21) and obese (n = 16) male Zucker rats were fed plain chow or chow containing 6 g DHEA/kg chow (0.6% wt/wt) from age 4 wk to 20 wk. Daily energy intakes and body weights were determined at least once weekly.
As expected, the lean and obese rats given DHEA exhibited less daily energy intake (kJ/d) and less weight gain than their respective controls of the same age. The lean rats given DHEA did not exhibit any difference in daily energy intake when determined relative to body weight (b.w.) (kJ x d-1 x g b.w.-1) compared to lean controls of the same metabolic body size, while the obese rats given DHEA exhibited less daily energy intake relative to b.w. (kJ x d-1 x g b.w.-1) compared to obese control of the same metabolic body size.
Though DHEA reduced total energy intake among the lean and obese Zucker rats, only the obese rats exhibited less energy intake relative to b.w. compared to controls of the same metabolic body size. Thus, DHEA may exert different effects on energy intake relative to b.w. in lean and obese Zucker rats and perhaps the lean Zucker rat is a better model for evaluating the metabolic effects of DHEA since it does not exhibit any effect on energy intake relative to b.w. compared to rats of the same metabolic body size.
Diabetes Obesity and Metabolism 08/1999; 1(4):233-9. · 5.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hyperactivity and hypoactivity of the HPA have been forwarded as of pathophysiological relevance in major depressive disorder and chronic fatigue syndrome (CFS), respectively.
This study examines cortisol levels in the two disorders, and also assesses levels of the adrenal androgens, dehydroepiandrosterone (DHEA) and its sulphate derivative (DHEA-S), and 17-alpha-hydroxyprogesterone; 15 subjects with CFS diagnosed according to CDC criteria, 15 subjects with DSM III-R major depression and 11 healthy subjects were compared.
DHEA and DHEA-S levels were significantly lower in the CFS compared to the healthy group; DHEA-S levels, but not DHEA, were lower in the depressives; cortisol and 17-alpha-hydroxyprogesterone did not differ between the three groups.
A potential role for DHEA, both therapeutically and as a diagnostic tool, in CFS, is suggested.
Journal of Affective Disorders 08/1999; 54(1-2):129-37. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Enterostatins [Val-Pro-Asp-Pro-Arg (VPDPR), Val-Pro-Gly-Pro-Arg (VPGPR), and Ala-Pro-Gly-Pro-Arg (APGPR)] are pentapeptides derived from the NH2-terminus of procolipase after tryptic cleavage and belong to the family of gut-brain peptides. Although enterostatin-like immunoreactivities exist in blood, brain, and gut, and exogenous enterostatins decrease fat appetite and insulin secretion in rats, the roles of these peptides in human obesity remain to be examined. To determine whether VPDPR and APGPR secretion is altered in obesity, serum VPDPR and APGPR levels were measured in 38 overnight-fasted subjects (body mass index, 17.9-54.7 kg/m2) before and after a meal. The mean fasting VPDPR in the serum of lean subjects was significantly lower than that in obese subjects [lean = 603 +/- 86 nmol/L (n = 17); obese, 1516 +/- 227 nmol/L (n = 21); P = 0.0023]. In addition, the rise in serum APGPR after a meal (postmeal/fasting ratio) was significantly higher in lean than in obese subjects [lean, 1.71 +/- 0.24 (n = 17); obese, 1.05 +/- 0.14 (n = 21); P = 0.0332]. The results of these studies show hyperenterostatinemia in obesity and a diminution in enterostatin secretion after satiety.