EFFECT OF HYPERLIPIDEMIA ON GLOMERULAR SCLEROSIS IN UNILATERAL NEPHRECTOMIZED RATS

The development of focal segmental glomerular sclerosis (FSGS) and its relation to hypertriglycemia were studied in unilateral nephrectomized rats. Group A (n=6), fed standard rat chow supplemented with 20% beef tallow and 0.6% cholic acid for 25 weeks, showed evidence of hypertriglycemia (109.4 ±4.3 mg/dl). Group B (n=7) was given the same rat chow as group A, but they did not have high serum levels of TG (66.4 ±2.3 mg/dl). Group C (n = 6) were the controls and their serum TG levels were 53.0 ±3.8 mg/dl. The incidence of FSGS and body weight was significantly higher in group A than in groups B (<0.01) and C (<0.05). In all three groups, rats with over a 4% FSGS revealed significantly high serum TG levels, proteinuria, and body weight, as compared with rats with less than 1% of FSGS. The serum cholesterol levels did not correlate with the incidence of FSGS. We tentatively conclude that hypertriglycemia induced by a diet rich in saturated fatty acid may play an importent role in the production and progression of FSGS.     

Associations between hypertriglyceridemia and serum ghrelin, adiponectin, and IL-18 levels in HIV-infected patients

HIV-related metabolic abnormalities include hypertriglyceridemia, hypercholesterolemia, insulin resistance, and diabetes mellitus. Recent studies suggest a role of ghrelin in promoting the deposition of triglycerides (TG) in the liver and regulating the metabolic action of adiponectin. Visceral fat is a key regulator of inflammation and it secretes proinflammatory cytokines (eg, interleukin-18, IL-18), with potential atherogenic activity. The aim of this study was to assay serum concentrations of ghrelin, adiponectin, and IL-18 in HIV+ patients, with and without hypertriglyceridemia, who were receiving highly active antiretroviral therapy (HAART). The 49 HIV+ patients were divided in 2 groups: 17 patients with serum TG concentration >200 mg/dl (group A) and 32 patients with normal serum TG concentration (group B). All subjects underwent viral and immunological evaluations and determinations of serum cholesterol, glucose, ghrelin, adiponectin, and IL-18. No differences of viral and immunological parameters were observed between the 2 groups. Serum levels of ghrelin were 768 +/- 596 pg/dl in group A and 470 +/- 248 pg/dl in group B (p = 0.01). Group A had lower serum adiponectin levels (8.4 +/- 3.6 microg/dl) than group B (18.2 +/- 10.1 microg/dl; p = 0.0001). Serum IL-18 levels were 455 +/- 199 pg/ml in group A and 258 +/- 233 pg/ml in group B (p = 0.005). The patients with hypertriglyceridemia showed a positive correlation between serum triglyceride and ghrelin levels (r = 0.51, p = 0.03). These findings suggest potential roles of ghrelin, adiponectin, and IL-18 in the pathogenesis of metabolic disorders in HIV-infected patients.     

Failure of angiotensin converting enzyme inhibition to affect the course of chronic puromycin aminonucleoside nephropathy.

The effects of the angiotensin converting enzyme (ACE) inhibitor enalapril on the proteinuria and degree of focal glomerular sclerosis hyalinosis (FSH) in chronic puromycin aminonucleoside nephropathy (PAN) were examined. Chronic PAN was induced in male Sprague-Dawley rats by seven subcutaneous injections of puromycin aminonucleoside (20 mg/kg) over 10 weeks (Groups I and II). Group II rats also received enalapril 10 mg/kg/day in the drinking water throughout the study (12 weeks). Group III rats served as age-matched controls. Proteinuria was similar in Groups I and II (35.5 +/- 9.7 versus 29.1 +/- 4.1 mg protein/mg creatinine, mean +/- SEM, P greater than 0.05). Serum creatinine remained unchanged in Group I, but rose from 0.7 +/- 0.04 to 1.2 +/- 0.1 mg/dl (mean +/- SEM, P less than 0.05) in Group II. FSH was 13.8% in Group I, 12.9% in Group II (P greater than 0.05), and 0.6% in Group III. There was no significant difference in glomerular lipid content and in immunofluorescence for rat albumin, fibrinogen, IgM, IgG, and C3 between Groups I and II. ACE activity was inhibited by 94% in serum, 83% in lungs, and 92% in kidneys; and blood pressure response to. Angiotensin I challenge was decreased by 50% in rats similarly treated with enalapril versus controls. In summary, proteinuria and glomerular sclerosis in this model are not affected by ACE inhibition.     

Apolipoproteins in rat cerebrospinal fluid: a comparison with plasma lipoprotein metabolism and effect of aging.

Cerebrospinal fluid (CSF) apo E concentrations, determined by a sensitive sandwich ELISA, were 411.3 +/- 76.0 and 454.3 +/- 51.8 micrograms/dl (mean +/- S.D.) for young rats (8-12 weeks old, n = 7) and old rats (36-40 weeks old, n = 10), respectively. Age-related increase, which was conspicuous in serum apo E (21.2 +/- 2.4 vs 60.9 +/- 14.1 mg/dl for young and old rats, respectively), was not observed in CSF apo E. CSF apo A-I concentrations, determined by ELISA, were extremely low in the both groups (less than 10 micrograms/dl). Neither CSF apo A-I nor CSF apo E correlated to any of the plasma lipoprotein components, indicating the presence of largely independent lipoprotein metabolism in the rat central nervous system. Apo E is present in CSF in the form of apo E-rich HDL1 with particle sizes similar to those of plasma E-rich HDL1.     

Cholesterol lipoproteins,triglycerides, rural-urban differences and prevalence of dyslipidaemia among males in Rajasthan

To develop profiles of serum cholesterol lipoproteins and triglycerides, influence of rural versus urban lifestyle in their levels and prevalence of dyslipidaemias, we studied cohorts of male population in Rajasthan. Fasting blood samples were obtained from 401 men (age range 20-73 years) randomly selected from a larger sample of 3397 during a comprehensive cardiovascular risk factor survey in rural (202 men) and urban (199 men) populations. Serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides (TG) were determined and correlated with age and anthropometric variables. The lipid levels were classified according to US National Cholesterol Education Program (NCEP) guidelines. The mean +/- SD levels in mg/dl were, total cholesterol 170.5 +/- 40, LDL cholesterol 102.1 +/- 36, HDL cholesterol 43.6 +/- 12 and TG 124.0 +/- 50. The mean levels in rural vs. urban population were total cholesterol 165 +/- 37 vs. 176 +/- 43 (p = 0.008), LDL cholesterol 97 +/- 33 vs. 108 +/- 39 (p = 0.003), HDL cholesterol 44 +/- 13 vs. 43 +/- 12 (p = 0.44) and TG 122 +/- 46 vs 126 +/- 55 (p = 0.41). There was significant positive correlation of age and body-mass index with total and LDL cholesterol and triglycerides but not with HDL cholesterol. When classified according to the NCEP guidelines high total cholesterol (> or = 240 mg/dl) and LDL cholesterol (> or = 160 mg/dl) was in 33 (8.3%). Borderline high total cholesterol (200-239) was in 64 (16%) and borderline high LDL cholesterol (130-159) in 55 (13.7%). Borderline high triglyceride (200-400 mg/dl) was in 33 (8.2%) and severe hypertriglyceridaemia in none. Low HDL cholesterol (< 35 mg/dl) was in 96 (23.9%) and protective level of HDL cholesterol (> or = 60 mg/dl) in 47 (11.7%). In urban as compared to rural men the prevalence of hypercholesterolaemia > 200 mg/dl (28% vs 22%) and hyper LDL cholesterolaemia (26% vs 18%) were significantly more.     

Low serum LDL cholesterol levels and the risk of fever, sepsis, and malignancy

Lipid lowering therapy of serum LDL cholesterol (LDL) has proved beneficial in reducing cardiovascular morbidity and mortality. Lately the recommended target LDL level in very high risk patients was reduced to <70 mg/dl, raising the question of what the price of such a low level will be. To elucidate this concern, we investigated the associations of low serum LDL cholesterol levels (< or = 70 mg/dl) and the incidences of fever, sepsis, and malignancy. Retrospective analysis of 203 patients' charts was carried out. Patients were divided into 2 groups: Group 1 (n = 79) had serum LDL levels < or = 70 mg/dl, while Group 2 (n = 124) had levels >70 mg/dl. The first group demonstrated increased odds of hematological cancer by more than 15-fold (OR 15.7, 95% CI 1.78-138.4, p = 0.01). Each 1 mg/dl increase in LDL was associated with a relative reduction of 2.4% in the odds of hematological cancer (OR 0.976, 95% CI 0.956-0.997, p = 0.026). Low LDL levels also increased the odds of fever and sepsis between the groups (OR 5.3, 95% CI 1.8-15.7, p = 0.02). In summary, low serum LDL cholesterol level was associated with increased risks of hematological cancer, fever, and sepsis.     

Differential effects of chow and purified diet on the consumption of sucrose solution and lard and the development of obesity

Obesity has been associated with increased consumption of sweetened beverages and a high-fat diet. We determined whether the composition of the dry pellet offered with liquid sucrose (LS) and lard influenced the development of obesity. We hypothesized that animals offered LS or LS and lard (choice), in addition to chow or purified low fat diet pellet (LFD; 10% fat), would gain more body fat than controls. We compared the effects of LFD vs. chow on voluntary consumption of LS and lard, serum triglyceride (TG), glucose, and body fat over 21 days. Male Sprague Dawley rats (n=10/group) were offered chow, chow+LS, chow choice, LFD, LFD+LS, LFD choice or solid high-sucrose diet (70% sucrose). Energy intakes of rats fed chow, LFD, and high-sucrose diets were similar. Energy intake was increased by 16% in chow+LS, 15% in LFD+LS, 11% in LFD choice, and 23% in chow choice rats. Chow choice rats consumed 142% more lard than LFD choice rats. Fasting glucose increased in all choice rats compared with the chow and high-sucrose diet rats. Fasting TG increased in LFD choice rats and were ~75% higher than those of chow, LFD, or high-sucrose rats. Chow choice had higher carcass fat than chow, chow+LS, and LFD groups however LFD choice was not different from their controls. Another experiment confirmed rats consumed 158% more lard when given chow choice compared to LFD choice. The diet offered to rats with free access to LS and lard influenced the development of obesity, sucrose and lard selection, and TG.     

Calcium and phosphorus deficiency in rats: effects on PTH and 1,25-dihydroxyvitamin D3.

Weanling male Holtzman rats were fed calcium.deficient, phosphorus-deficient, or control diets for 8 wk. Parathyroid hormone (PTH) was measured by radioimmunoassay, and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) by a competitive binding assay. Rats fed the calcium-deficient diet (0.01% calcium, 0.6% phosphorus) became mildly hypocalcemic after 6 days. Serum calcium levels reached 5.5 +/- 0.4 mg/dl (mean +/- SD) in 5 wk (control 10.3 +/- 0.4 mg/dl). PTH increased from 285 +/- 112 to 3658 +/- 428 pg/ml within 6 wk. Maximum serum levels of 1,25(OH)2D3 (111.8 +/- 17.3 vs. control 11.4 +/- 3.8 ng/dl) were reached at 3 wk and thereafter declined to 44.6 +/- 14.0 ng/dl. In rats fed the phosphorus-deficient diet (0.6% calcium, 0.04% phosphorus), serum phosphorus fell within 24 h from 9.1 +/- 0.6 to 3.2 +/- 0.1 mg/dl, recovered to 5.6 +/- 0.4 mg/dl for 2-3 days, and then declined again. Serum calcium reached a maximum of 14.4 +/- 0.4 mg/dl at day 2 (control 10.8 +/- 0.5 mg/dl) and then slowly declined. PTH decreased within 24 h from 243 +/- 59 to 36 +/- 0 pg/ml in phosphorus-depleted rats. Serum levels of 1,25(OH)2D3 increased within 24 h and remained elevated after 6 wk of phosphorus deprivation (61.2 +/- 11.7 ng/dl vs. control 18.3 +/- 0.4 ng/dl).     

Chronic effects of type 2 diabetes mellitus on cardiac muscle contraction in the Goto-Kakizaki rat

Type 2 diabetes mellitus accounts for more than 90% of all cases of diabetes mellitus, and cardiovascular complications are the major cause of mortality and death in diabetic patients. The chronic effects of type 2 diabetes mellitus on heart function have been investigated in the Goto-Kakizaki (GK) rat. Experiments were performed in GK rats and age-matched Wistar control rats at 18 months of age. The progressive effects of diabetes on glucose metabolism were monitored periodically by application of the glucose tolerance test. Ventricular action potentials were measured in isolated, perfused heart. Shortening and intracellular Ca(2+) were measured in electrically stimulated ventricular myocytes. The GK rats displayed mild fasting hyperglycaemia and progressively worsening glucose tolerance. At 18 months of age and 180 min after intraperitoneal injection of glucose (2 g (kg body weight)(-1)), blood glucose was 436 +/- 47 mg dl(-1) in GK rats compared with 153 +/- 18 mg dl(-1) in control animals. Heart weight to body weight ratio was significantly increased in GK rats (4.10 +/- 0.09 mg g(-1), n = 5) compared with control animals (3.36 +/- 0.22 mg g(-1), n = 4). Spontaneous heart rate was slightly reduced in GK rats compared with control rats. Although the amplitude of shortening was not altered, the amplitude of the Ca(2+) transient was significantly increased in myocytes from GK rats (0.78 +/- 0.11 ratio units) compared with control rats (0.50 +/- 0.06 ratio units). Despite progressively worsening glucose metabolism, at 18 months of age the contractile function of the heart appears to be well preserved.     

Serum lipid and apolipoprotein levels in patients with chronic pancreatitis]

Serum lipid and apolipoprotein (apo A-I, A-II, A-IV, B, C-II, C-III, E and H) levels were determined in 26 patients with chronic pancreatitis without complications such as liver disease or diabetes mellitus. These patients were divided into two groups, CP-I (n = 16) and CP-II (n = 10), according to the clinical criteria for chronic pancreatitis. HDL-cholesterol and apo A-I levels in CP-I and CP-II groups significantly decreased compared to those in sex- and age-matched healthy controls (p less than 0.05), whereas there were not significant differences in triglyceride and total cholesterol levels between these groups and controls. On the other hand, apo A-IV levels in CP-I and CP-II were 7.1 +/- 1.0 mg/dl and 8.3 +/- 1.5 mg/dl, respectively and these values were significantly lower than 11.2 +/- 1.8 mg/dl in controls (p less than 0.001). In this study, the serum lipids apparently showed normal levels in patients with chronic pancreatitis who had no severe complication, and the markedly low apo A-IV levels in these patients were considered to be mainly due to the decrease of lipid absorption from the intestine.     

Effects of metabolic acidosis on PTH and 1,25(OH)2D3 response to low calcium diet

To study the effects of chronic metabolic acidosis on the metabolism of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] rats were given either a low calcium diet (LCD) (0.002% calcium) or chow (1.2% calcium); ammonium chloride (NH4Cl) was added (1 or 1.5%) to the drinking water of some rats eating LCD or chow while others served as nonacidotic controls. LCD increased circulating 1,25(OH)2D3 levels from 46 +/- 14 to 204 +/- 24 pg/ml (P less than 0.001) in the absence of NH4Cl; 1.5% NH4Cl prevented the increase in 1,25(OH)2D3 (25 +/- 6 vs. 27 +/- 8 pg/ml (P, NS) but 1% NH4Cl did not (50 +/- 12 vs. 161 +/- 23 pg/ml; P less than 0.001). Acidosis suppressed neither serum immunoreactive parathyroid hormone (PTH) nor urine cAMP response to LCD. Although total serum calcium and phosphorus showed no regular changes with NH4Cl, acidosis raised blood ionized calcium in rats fed either chow or LCD, and serum 1,25(OH)2D3 levels were inversely correlated with ionized calcium (r = 0.714; P less than 0.001) during LCD. Chronic NH4Cl acidosis prevented serum 1,25(OH)2D3 from rising during LCD, independent of changes in PTH secretion, cAMP generation, or serum phosphorus. The absence of a 1,25(OH)2D3 response may be due to increased ionized calcium produced by acidosis.     

Polymorphisms at the SRBI locus are associated with lipoprotein levels in subjects with heterozygous familial hypercholesterolemia

Scavenger receptor, class B, type 1 (SRBI) is a promising candidate gene involved in the pathophysiology of atherosclerosis. We have examined the association of three common polymorphisms at the SRBI locus in 77 subjects who were heterozygous for familial hypercholesterolemia (FH). The alleles represented by polymorphisms in exon 1 and exon 8 were associated with variation in plasma concentrations of fasting triglyceride (TG). Mean plasma TG concentrations for homozygotes for the most common allele, and for heterozygotes and homozygotes for the less common allele were 85 +/- 6, 111 +/- 9 and 135 +/- 22 mg/dl (p = 0.011) for exon 1, and 96 +/- 11, 86 +/- 6 and 134 +/- 13 mg/dl (p = 0.007) for exon 8, after adjustment for age, sex and body mass index. In addition, the exon 8 polymorphism was associated with increased total cholesterol (320 +/- 15, 340 +/- 8 and 388 +/- 18 mg/dl, p = 0.015), very low density lipoprotein (VLDL) cholesterol (18 +/- 2.9, 15.7 +/- 1.6 and 33.4 +/- 3.9 mg/dl, p < 0.001) and low density lipoprotein (LDL) cholesterol (251 +/- 15, 270 +/- 8 and 312 +/- 10 mg/dl, p = 0.041) concentrations. In agreement with animal studies, our data also suggest a role for the SRBI in the metabolism of apolipoprotein B (apoB)-containing lipoproteins in humans. This pathway may constitute a backup mechanism to LDL receptor-mediated pathways for the catabolism of these lipoproteins, which could be particularly relevant in subjects with high levels of apoB-containing lipoproteins, such as those occurring in patients with FH.     

Influence of apolipoprotein B signal peptide insertion/deletion polymorphism on serum lipids and apolipoproteins in a Chinese population

Insertion/deletion polymorphism of the apo B gene encoding signal peptide and its influence on serum lipids and apolipoproteins was studied in 269 Chinese of both sexes in Singapore. The frequency of the Del allele was found to be 0.20, which is significantly lower than that in Caucasians (France) (0.34). The distribution of genotypes of ins/del polymorphism was at Hardy-Weinberg equilibrium in this population. There was an excess of individuals with the deletion allele in hypercholesterolemic subjects compared to those with normal cholesterol levels (P less than 0.05). All the lipid and apolipoprotein values were regressed for age, sex and BMI by multiple regression analysis. Individuals with one or two del alleles had significantly higher levels of serum total cholesterol (248.8 +/- 13.0 and 255.4 +/- 20.4 mg/dl, respectively) compared to those in individuals with only the Ins allele (218.4 +/- 7.8 mg/dl) (P less than 0.05). Serum LDL cholesterol level was also significantly higher in individuals with del allele (173.4 +/- 11.7 mg/dl) compared to that in those without the del allele (141.1 +/- 7.4 mg/dl) (P = 0.02). The percentages of sample variance of different lipid traits explained by apo B signal peptide polymorphism were estimated by analysis of variance (ANOVA) with sex, age and BMI as covariates. 2.3% of variability of serum total cholesterol (F = 3.27, P = 0.040) and 2.8% of LDL cholesterol (F = 3.87, P = 0.023) could be explained by the ins/del polymorphism of the apo B signal peptide gene.     

Cardiovascular risk factor profiles and angiography results in young patients

There is a clear correlation between the incidence of coronary artery disease and existing cardiovascular risk factors. Therefore, it is a matter of interest if there is an accumulation of risk factors in younger patients with premature coronary artery disease compared to those without. We evaluated 1708 consecutive patients who underwent coronary angiography at our institution between August 2001 to February 2002; 85 symptomatic patients under the age of 46 were included in our analysis. In 46 patients (54.1%)--mean age 41.5 +/- 3.6 years--a coronary artery disease was documented, in 39 patients (45.9%)--mean age 39.9 +/- 5.6 years (n.s.)--normal coronary arteries were shown at angiography. Regarding the cardiovascular risk factors in young patients with coronary artery disease compared to young patients without we found a family history of premature coronary artery disease in 54.5% versus 43.6% (n.s.), hypercholesterolemia in 56.5% versus 53.8% (n.s.), LDL cholesterol of 138 +/- 40 mg/dl versus 123.3 +/- 27 mg/dl (s.), HDL cholesterol of 39 +/- 9 mg/dl versus 45.6 +/- 12.6 mg/dl (s.), serum triglycerides of 194.6 +/- 114.9 mg/dl versus 162.1 +/- 98.4 mg/dl (n.s.), diabetes mellitus in 15.2% versus 10.3% (n.s.), hypertension in 45.7% versus 46.4% (n.s.), body mass index > 24.9 kg/m2 in 67.4% versus 69.2% (n.s.), cigarette smoking in 54.6% versus 56.4% (n.s.). And finally, a minimum of two of those risk factors was found in 93.5% versus 87.2% (n.s.). Due to the high prevalence of cardiovascular risk factors in both groups it is impossible to reliably predict the incidence of coronary artery disease from those risk factors. This has to be considered while deciding about the indication for coronary angiography.     

Exaggerated response to gentamicin-induced nephrotoxicity in Sprague-Dawley rats: identification of a highly sensitive outlier population

A number of factors have been shown to predispose patients treated with aminoglycosides to nephrotoxicity. In a previous study in our laboratory investigating the interaction of prior renal dysfunction with gentamicin toxicokinetics, 9.4% of rats in all treatment groups were relatively more sensitive to gentamicin-induced nephrotoxicity. To determine if these outliers had an underlying disease or physiological abnormality, serum was collected from 99 Sprague-Dawley rats prior to daily treatment with 75 mg/kg gentamicin for seven days. Urea nitrogen, creatinine, Na, K, Ca, Mg, P, total protein, albumin, aspartate transaminase, serum osmolality, total white and red blood cell count, hematocrit, hemoglobin, blood gases, and thyroxine were measured. Blood was collected one and four hours after the first dose of gentamicin for pharmacokinetic analysis. Elevations in post-treatment creatinine and nitrogen were significantly greater in the outliers (4.10 +/- 0.24 mg/dl (n = 12) vs 1.92 +/- 0.06 mg/dl (n = 87) and 146.4 +/- 7.2 mg/dl (n = 12) vs 71.5 +/- 2.0 mg/dl (n = 87); both p = 0.0001) and served as criteria for identifying this subgroup. Post-treatment creatinine and urea nitrogen were not normally distributed in the entire study population. However, when the population was divided into normal and sensitive subgroups, both subgroup values were normally distributed. The gentamicin pharmacokinetic profiles were similar in both groups. Postmortem histopathology showed significant increases in tubular casts and tubular necrosis (p = 0.01) in the sensitive rats, compared to the normally responding subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of serum HDL-cholesterol and LCAT levels with the fraction of ionized magnesium in children.

Correlation of serum lipids and apolipoprotein levels with serum total magnesium concentration and whole blood ionized magnesium level was determined in 47 children (14 female and 33 male; mean age, 8.7 +/- 4.2 years). Mean serum concentration of magnesium was 2.19 +/- 0.19 mg/dl, whole blood concentration of ionized magnesium 1.23 +/- 0.08 mg/dl, and fraction of ionized magnesium (ratio of whole blood ionized magnesium to serum total magnesium) 0.56 +/- 0.04. Neither serum total magnesium level nor whole blood ionized magnesium level had any correlation with serum albumin, lipid, and apolipoprotein levels. However, the fraction of ionized magnesium was significantly correlated with HDL-cholesterol (n = 46, r = 0.31, p = 0.0345), apolipoprotein A-1 (n = 41, r = 0.39, p = 0.0124), and lecithin-cholesterol acyltransferase (LCAT) (n = 20, r = 52, p = 0.0184). These results suggest that fraction of ionized magnesium is more closely linked to serum HDL-cholesterol and LCAT level than with the serum total magnesium level or whole blood ionized magnesium.     

Dehydroepiandrosterone-mediated decrease in caloric intake by obese Zucker rats is not due to changes in serum entrostatin-like immunoreactivity

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.     

Status of selenium, vitamin E, and vitamin A among Saudi adults: potential links with common endemic diseases

This study was designed to determine the status of selenium, dl-alpha-tocopherol, and all-trans-retinol in adults living in Al-Kharj district using serum and toenail samples, and to look for possible association between these parameters and the etiology of endemic diseases in the same area. For this purpose, we examined a cross section of samples of 743 healthy Saudi adults on routine visits to the Primary Health Care Unites (PHCUs) for different common health problems. The arithmetic mean for selenium, dl-alpha-tocopherol, and all-trans-retinol in serum and toenail selenium levels were 107.045 +/- 23.045 microg/l (n = 743, range 52.600-210.120 microg/l), 1.053 +/- 0.324 mg/dl (n = 737, range 0.29-3.42 mg/dl), 52.561 +/- 25.671 microg/dl (n = 743, range 11.20-400.85 microg/dl), and 0.634 +/- 0.221 microg/g (n = 691, range < DL - 1.797 microg/g), respectively. The average serum selenium concentration seems to be satisfactory and compares favourably with high selenium intake countries. Although none of our participants exhibited serum selenium deficiency (< 45 microg/l), 41% of our participants had toenail selenium < 0.56 microg/g reported low levels in the previous study. The mean serum dl-alpha-tocopherol concentrations fall within the upper limit of the normal range of > 0.698-1.981 mg/dl for alpha-tocopherol as found in previous studies. On the other hand, the mean serum all-trans-retinol is higher than the normal range (20-30 microg/dl). None had exhausted retinol stores trans-retinol and MDA levels in the serum was found as a sign of peroxidative lipid damage, confirming the role of vitamin A in reducing oxidative stress. Our data also revealed a link between the status of selenium, dl-alpha-tocopherol and all-trans-retinol and a number of health problems. However, these observations need larger epidemiological studies for further confirmation.     

Relationships of soluble APO-1 (Fas/CD95) concentrations, obesity, and serum lipid parameters in healthy adults

To investigate the relationships of apoptosis with obesity and lipid parameters, we measured serum soluble APO-1 (sAPO-1) concentrations, body mass index (BMI), and serum lipid profiles in 176 healthy adults. Serum sAPO-1 levels were measured by enzyme immunoassay. There were no significant differences in mean sAPO-1 concentrations between men and women, nor between subjects with and without obesity. However, women with high-density lipoprotein cholesterol (HDL-C) <50.2 mg/dl exhibited significantly higher sAPO-1 concentrations than those with HDL-C >50.2 mg/dl (ie, 45.6 +/- 10.4 pg/ml vs 31.5 +/- 11.3 pg/ml, p <0.05). Serum sAPO-1 concentrations averaged 46.8 +/- 10.7 pg/ml in women with serum triglyceride >137.4 mg/dl, which was significantly above the mean value (32.6 +/- 12.0 pg/ml, p <0.05) in those with serum triglyceride <137.4 mg/dl. Men with elevated sAPO-1 concentrations showed significantly higher waist-to-hip ratio (WHR) and total body fat (TBF) compared to those with diminished sAPO-1 levels, although no differences were noted in mean values of lipid profiles between the 2 groups of men. Serum sAPO-1 concentrations correlated significantly with HDL-C (r = - 0.41, p <0.05) and triglyceride (r = 0.35, p <0.05) in women and WHR (r = 0.25, p <0.05) and TBF (r = 0.21, p <0.05) in men. In conclusion, serum sAPO-1 appears to have an important relationship to serum lipid levels and body adiposity in healthy adults.     

The increase in hepatic uncoupling by fenofibrate contributes to a decrease in adipose tissue in obese rats

Fenofibrate is a drug that has been suggested to inhibit weight gain by increasing the catabolism of fatty acid in the hepatic mitochondria. We hypothesized that fenofibrate induces an increase in energy expenditure in the hepatic mitochondria, which results in the reduction of adipose tissue. In this study we measured hepatic uncoupling protein (UCP)-2, -3, core temperatures and abdominal fat composition with MRI in Otsuka Long-Evans Tokushima Fatty rats. The fenofibrate group (n=7) was fed fenofibrate (320 mg/kg) mixed chow. The control group (n=7) was fed chow only. The body weight (531.6+/-7.6 g) of the fenofibrate group was significantly lower than that (744.3+/-14.9 g) of the control group (p<0.005). The areas of visceral and subcutaneous fat in the fenofibrate group (11.0+/-0.9 cm(2), 4.2+/-0.3 cm(2)) were significantly less than those in the control group (21.0+/-0.7 cm(2), 7.4+/-0.4 cm(2)) (p=0.046, respectively). The esophageal and rectal temperatures of the fenofibrate group (37.7+/-0.1 degrees C, 33.1+/-0.2 degrees C) were significantly higher than those of the control group (37.3+/-0.1 degrees C, 32.2+/-0.1 degrees C) (p=0.025, p=0.005). There was de novo expression of UCP-3 in the liver of the fenofibrate group. These data suggest that increased energy dissipation, via hepatic UCP-3 by fenofibrate, contribute to decreased weight gain in obese rats.