Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats

Background. Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Methods. Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70-80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx -) were measured. Concentration- response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting. Results. High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl). Neither high caloric diet nor RT modified NO x - levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels. Conclusion. The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation. © 2008 de Moraes et al; licensee BioMed Central Ltd.

Exercise counteracts fatty liver disease in rats fed on fructose-rich diet

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Decreased rate of protein synthesis, caspase-3 activity, and ubiquitin-proteasome proteolysis in soleus muscles from growing rats fed a low-protein, high-carbohydrate diet

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Changes of glycogen content in liver, skeletal muscle, and heart from fasted rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Impact of early fructose intake on metabolic profile and aerobic capacity of rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lactose load enhances the growth of the small intestine in rats

The present study was undertaken to elucidate the controversial issue regarding the small intestinal structural adaptation, in lactose fed rats. Three study groups were used. One experimental fed 60% lactose and two controls in which the lactose was substituted for similar amount of starch. One of them was fed ad libitum and another a limited amount of food to match the body weight of lactose group. The weight, length of the intestine and intestinal mucosal DNA and protein were determined at days 2, 5, 10 and 30 of the experiment. As compared to starch fed ad libitum controls, animals fed 60% lactose diet ate similar amount of food, grew at a slower rate and weighed 16,7% less at the end of the experiment. In contrast to retarded gain in body weight, small intestinal mucosa of these animals contained more DNA (22,5%) and protein (37,5%) than that of controls. These changes were paralleled by increase in length (17%) and weight of the intestine (24,2%). Therefore, the results of the present study confirmed the findings that the small intestine increases in size in response to lactose feeding and that this occurs in the abscense of hyperphagia. It was further demonstrated that this increase was due both to mucosal cell hyperplasia and hypertrophy.

Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

Background: It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle.Methods: To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein):pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine):leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption.Results: Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups.Conclusions: Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

EFFECT OF CAFFEINE ON THE METABOLISM OF RATS EXERCISING BY SWIMMING

Several studies have demonstrated that caffeine improves endurance exercise performance but the mechanisms are not fully understood. Possibilities include increased free fatty acid (FFA) oxidation with consequent sparing of muscle glycogen as well as enhancement of neuromuscular function during exercise. The present study was designed to investigate the effects of caffeine on liver and muscle glycogen of 3-month old, male Wistar rats (250-300 g) exercising by swimming. Caffeine (5 mg/kg) dissolved in saline (CAF) or 0.9% sodium chloride (SAL) was administered by oral intubation (1 mu l/g) to fed rats 60 min before exercise. The rats (N = and-IO per group) swam bearing a load corresponding to 5% body weight for 30 or 60 min. FFA levels were significantly elevated to 0.475 +/- 0.10 mEq/l in CAF compared to 0.369 +/- 0.06 mEq/l in SAL rats at the beginning of exercise. During exercise, a significant difference in FFA levels between CAF and SAL rats was observed at 30 min (0.325 +/- 0.06 vs 0.274 +/- 0.05 mEq/l) but not at 60 min (0.424 +/- 0.13 vs 0.385 +/- 0.10 mEq/l). Blood glucose showed an increase due to caffeine only at the end of exercise (CAF = 142.1 +/- 27.4 and SAL = 120.2 +/- 12.9 mg/100 ml). No significant difference in liver or muscle glycogen was observed in CAF as compared to SAL rats, at rest or during exercise. Caffeine increased blood lactate only at the beginning of exercise (CAF = 2.13 +/- 0.2 and SAL = 1.78 +/- 0.2 mmol/l). These data indicate that caffeine (5 mg/kg) has no glycogen-sparing effect on rats exercising by swimming even though the FFA levels of CAF rats were significantly higher at the beginning of exercise.

Chronic alcohol intake upregulates hepatic expression of carotenoid cleavage enzymes and PPAR in rats

Excessive and chronic alcohol intake leads to a lower hepatic vitamin A status by interfering with vitamin A metabolism. Dietary provitamin A carotenoids can be converted into vitamin A mainly by carotenoid 15,15′-monooxygenase 1 (CMO1) and, to a lesser degree, carotenoid 9′10′-monooxygenase 2 (CMO2). CMO1 has been shown to be regulated by several transcription factors, such as the PPAR, retinoid X receptor, and thyroid receptor (TR). The regulation of CMO2 has yet to be identified. The impact of chronic alcohol intake on hepatic expressions of CMO1 and CMO2 and their related transcription factors are unknown. In this study, Fischer 344 rats were pair-fed either a liquid ethanol Lieber-DeCarli diet (n = 10) or a control diet (n = 10) for 11 wk. Hepatic retinoid concentration and expressions of CMO1, CMO2, PPARγ, PPARα, and TRβ as well as plasma thyroid hormones levels were analyzed. We observed that administering alcohol decreased hepatic retinoid levels but increased mRNA concentrations of CMO1, CMO2, PPARγ, PPARα, and TRβ and upregulated protein levels of CMO2, PPARγ, and PPARα. There was a positive correlation of PPARγ with CMO1(r = 0.89; P<0.0001) and both PPARγ and PPARα with CMO2 (r = 0.72, P< 0.001 and r = 0.62, P< 0.01, respectively). Plasma thyroid hormone concentrations did not differ between the control rats and alcohol-fed rats. This study suggests that chronic alcohol intake significantly upregulates hepatic expression of CMO1 and, to a much lesser extent, CMO2. This process may be due to alcohol-induced PPARγ expression and lower vitamin A status in the liver. © 2010 American Society for Nutrition.

Long-term ethanol consumption promotes hepatic tumorigenesis but impairs normal hepatocyte proliferation in rats

Chronic and excessive alcohol consumption has been related to an increased risk of several cancers, including that of the liver; however, studies in animal models have yet to conclusively determine whether ethanol acts as a tumor promoter in hepatic tumorigenesis. We examined whether prolonged alcohol consumption could act as a hepatic tumor promoter after initiation by diethylnitrosamine (DEN) in a rat model. Male Sprague-Dawley rats were injected with 20 mg DEN/kg body weight 1 wk before introduction of either an ethanol liquid diet or an isoenergic control liquid diet. Hepatic pathological lesions, hepatocyte proliferation, apoptosis, PPARα and PPARγ, and plasma insulin-like growth factor 1 (IGF-1) levels were assessed after 6 and 10 mo. Mean body and liver weights, plasma IGF-1 concentration, hepatic expressions of proliferating cellular nuclear antigen and Ki-67, and cyclin D1 in ethanol-fed rats were all significantly lower after 10 mo of treatment compared with control rats. In addition, levels of hepatic PPARγ protein, not PPARα, were significantly higher in the ethanol-fed rats after prolonged treatment. Although ethanol feeding also resulted in significantly fewer altered hepatic foci, hepatocellular adenoma was detected in ethanol-fed rats at 10 mo, but not in control rats given the same dose of DEN. Together, these results indicate that chronic, excessive ethanol consumption impairs normal hepatocyte proliferation, which is associated with reduced IGF-1 levels, but promotes hepatic carcinogenesis. © 2011 American Society for Nutrition.

The influence of temporal food restriction on the performance of isolated cardiac muscle

In this study we assessed the mechanical function of isolated left ventricular papillary muscles from 60 day-old male Wistar-Kyoto rats (WKY) subjected to different periods of food restriction (FR). The food-restricted animals (R) were fed 50% of the amount of diet consumed by the ad Libitum-fed rats (C). The cardiac muscles were studied after 30, 60, and 90 days (R-30, R-60 and R-90) of FR. The effect of FR on myocardial collagen concentration was also evaluated. The parameters from the three control groups that were statistically identical were combined and the control pool group (CP) was formed. The left ventricular weight-to-body weight ratio was lower in the R-30 and higher in the R-60 and R-90 in relation to their control groups. Hydroxyproline concentration was higher only in R-90 compared to CP and R-30. Myocardial mechanical function was the same in the C groups. The comparisons between CP and FR groups showed that: the muscles of R-30 presented increased resting tension and maximum rate of tension decline, and decreased velocity of shortening; the muscles of R-60 and R-90 groups showed a prolongation of the time to peak tension (TPT) and the time to peak shortening (TPS); and R-30 had an increased time from peak tension to 50% relaxation (RT1/2). Increases in TPT, TPS, and RT1/2 in groups R-60 and R-90 were significant in relation to R-30. In conclusion, while FR for 30 days produces disparate effects on myocardial performance, FR for 60 and 90 days prolongs the contraction period. The change of relaxation time in R-90 might be related to the increased myocardial collagen content. (C) 2001 Elsevier B.V. All rights reserved.