Chronic administration of iron and copper potentiates adipogenic effect of high fat diet in Wistar rats

The primary objective of this research project is explore a possible adipogenic effect of iron and/or copper in albino Wistar rats kept on standard (STD) and high-fat (HFD) diets. The female Wistar rats in the study were divided into eight experimental groups (n = 6). Rats maintained on STD and HFD received 3 mg/l FeSO₄·7H₂O, 4.88 mg/l CuSO₄ and a combination of 1.5 mg/l FeSO₄·7H₂O and 2.44 mg/l CuSO₄ with drinking water. Control groups were kept on STD and HFD and received pure water without metal salts. Consumption of iron and copper in the groups of rats maintained on an STD did not produce a significant increase in weight, adipose tissue content or body mass index. However, the adipocyte size and infiltration were increased in the adipose tissue of STD-fed rats receiving a mixture of iron and copper with drinking water. The rats fed iron and copper and, especially, their combination on a HFD background had a significantly higher weight gain, adipose tissue content, morphometric parameters values and adipocyte size compared to STD- and HFD-fed controls. Iron and copper consumption produced their accumulation in the rats’ adipose tissue. Moreover, the studied metals reduced adipose tissue concentration of chromium and vanadium. The lipoprotein profile and serum oxidative stress biomarkers were affected in the rats receiving the metals and STD. Hyperglycemia was observed in the rats receiving the studied metals on HFD-background. Based on the analysis of the test subjects, the study suggests that iron and copper administration, especially combined, may potentiate adipogenic effect of HFD.     

Effects of selenium on endothelial dysfunction and metabolic profile in low dose streptozotocin induced diabetic rats fed a high fat diet

Endothelial dysfunction develops as a result of oxidative stress and is responsible for diabetic vascular complications. We investigated the effects of selenium on endothelial dysfunction and oxidative stress in type 2 diabetic rats. Male Wistar rats were divided into five groups: controls, untreated diabetics, and diabetics treated with 180, 300, 500 mcg/kg selenium each day. Diabetes was induced by a single intraperitoneal injection of low dose streptozotocin to rats fed a high fat diet. Endothelium-dependent and -independent relaxations were measured in the thoracic aorta. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and endothelial nitric oxide synthase (eNOS) mRNA expressions were analyzed using real-time polymerase chain reaction (RT-PCR). Fasting blood glucose, lipid profile, lipid oxidation, insulin and nitric oxide were measured in blood samples. Malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase levels were measured in liver samples. RT-PCR showed that selenium reversed increased NADPH oxidase expression and decreased eNOS expression to control levels. Selenium also improved the impairment of endothelium-dependent vasorelaxation in the diabetic aorta. Selenium treatment significantly decreased blood glucose, cholesterol and triglyceride levels, and enhanced the antioxidant status in diabetic rats. Our findings suggest that selenium restores a normal metabolic profile and ameliorates vascular responses and endothelial dysfunction in diabetes by regulating antioxidant enzyme and nitric oxide release.     

Reduced CCK signaling in obese-prone rats fed a high fat diet

Deficits in satiation signaling during obesogenic feeding have been proposed to play a role in hyperphagia and weight gain in animals prone to become obese. However, whether this impaired signaling is due to high fat (HF) feeding or to their obese phenotype is still unknown. Therefore, in the current study, we examined the effects of CCK-8 (0.5, 1.0, 2.0, and 4.0 μg/kg) on suppression of food intake of HF-fed obese prone (OP) and resistant (OR) rats. Additionally, we determined the role of endogenous CCK in lipid-induced satiation by measuring plasma CCK levels following a lipid gavage, and tested the effect of pretreatment with devazepide, a CCK-1R antagonist on intragastric lipid-induced satiation. Finally, we examined CCK-1R mRNA levels in the nodose ganglia. We show that OP rats have reduced feeding responses to the low doses of exogenous CCK-8 compared to OR rats. Furthermore, OP rats exhibit deficits in endogenous CCK signaling, as pretreatment with devazepide failed to abolish the reduction in food intake following lipid gavage. These effects were associated with reduced plasma CCK after intragastric lipid in OP but not OR rats. Furthermore, HF feeding resulted in downregulation of CCK-1Rs in the nodose ganglia of OP rats. Collectively, these results demonstrate that HF feeding leads to impairments in lipid-induced CCK satiation signaling in obese-prone rats, potentially contributing to hyperphagia and weight gain.     

Steady state changes in mitochondrial electrical potential and proton gradient in perfused liver from rats fed a high fat diet

In this work the protonmotive force (p), as well as the subcellular distribution of malate, ATP, and ADP were determined in perfused liver from rats fed a low fat or high fat diet, using density gradient fractionation in non acqueous solvents.Rats fed a high fat diet, despite an enhanced hepatic oxygen consumption, exhibit similar p to that found in rats fed a low fat diet, but when we consider the two components of p, we find a significant decrease in mitochondrial/cytosolic pH difference (pH_m) and a significant increase in mitochondrial membrane potential (_m) in rats fed a high fat diet compared to rats fed a low fat diet, which tend to compensate each other. In rats fed a high fat diet the concentration ratio of malate and ATP/ADP does not reflect the changes in pH_m and _m, which represent the respective driving force for their transport.The findings are in line with an increase in substrate supply to the respiratory chain which is, however, accompanied by a higher energy turnover in livers from HFD rats. By this way the liver could contribute to the lack of weight gain from the high caloric intake in HFD rats.     

Antiatherogenic effect of taurine in high fat diet fed rats

The role of taurine on atherogenesis induced by high fat diet in rats, a species which depends entirely on taurine for conjugation of bile acids has been investigated. Wistar male rats were fed on (p.o.) taurine in addition to high fat diet (11% coconut oil w/w) for 6 months. High fat diet caused significant increase of serum total cholesterol (2 fold), serum triglycerides (92.6%), LDL cholesterol (92.3%) and body weight gain (2.8 fold). Taurine administration significantly reduced serum cholesterol (37%), triglycerides (94.5%), LDL cholesterol (34%), body weight (46%). It also significantly reduced aortic cholesterol and thiobarbituric acid reactive substances and there was a significant increase of reduced glutathione. Taurine significantly increased fecal bile acids which may have resulted in significant decrease of serum cholesterol. Aortic lesion index was significantly decreased in the taurine administered group suggesting the antiatherogenic effect of taurine. It is concluded that taurine attenuated the atherogenesis possibly by its hypocholesterolemic and antioxidant property.     

Effect of prolonged high salt diet on atrial natriuretic factor in rats

Normotensive Sprague-Dawley rats were given 8% NaCl for 5 weeks. This salt load did not affect their blood pressure nor hematocrit, and plasma atrial natriuretic factor (ANF) showed no change at 3 weeks but decreased after 5 weeks of the experimental period when compared with control rats. The responsiveness of particulate guanylate cyclase and formation of cGMP in ANF target organs suggested an augmented baseline activity of the cGMP system but its relative hyporesponsiveness to exogenous ANF following prolonged salt loading. Decreased plasma ANF levels cannot be explained by its altered production since atrial levels of the peptide were comparable in rats with or without salt loading. Atrial ANF mRNA was unaffected by the salt regimen. This study demonstrates that plasma ANF does not increase during long-term NaCl loading and even decreases after 5 weeks of 8% NaCl. The changes in plasma ANF are associated with changes in the functional state of ANF receptors coupled to particulate guanylate cyclase, but in the opposite direction than expected from lowered plasma ANF. Thus, ANF may not play a significant role in the regulation of sodium excretion in response to prolonged high salt consumption or, if it does, it is not reflected by expected changes in its plasma levels.     

High fat and high fructose diet induced intracranial atherosclerosis and enhanced vasoconstrictor responses in non-human primate

The present study examined the effect of high fat and high fructose (HFF) diet on the development of atherosclerosis and vascular contractile responses in the cerebral artery and thoracic aorta in non-human primates. Female cynomolgus monkeys (age: 3 to 4 years) were divided into normal control diet (N=5) and HFF diet groups (N=5). Twenty-eight weeks after feeding the HFF diet, total cholesterol and low-density lipoprotein-cholesterol in serum were significantly increased in the HFF diet group compared to the control group. The ultrastructural analyses of the basilar artery and aorta demonstrated the infiltration of lipid-laden foam cells and the appearance of lipid droplet-filled smooth muscle cells in the monkeys fed with the HFF diet. In terms of vascular reactivity, there was significantly greater vasoconstriction of the aorta and basilar artery in response to 5-hydroxytryptamine in the HFF diet group compared to the normal diet-fed group. In addition, KCl-induced vasoconstriction of the basilar arteries was also significantly enhanced in the HFF diet group compared to the normal diet-fed monkeys. In all, our present study has demonstrated that changes in the vascular responsiveness of the cerebral artery and its cellular architecture may manifest into cerebrovascular complications consistent with a pathological state normally observed with the onset and progression of atherosclerosis.     

Electrical activity of the amygdala and the septum of rats on a high fat or a high protein diet

The authors studied biopotentials in the region of the amygdala and the septum of rats fed on a standard, high protein or high fat diet. During the first 3-6 days after changing from the standard to the high protein or high fat diet, a decrease in the amplitude of electrical activity was found in both the regions in question. After 3 days on the high fat or the high protein diet, an increase was found in the frequency of electrical activity in the amygdala or the septum, according to the type of diet. A study of the amplitude of electrical activity showed that the electrical potential in the septum was always lower than in the amygdala. The frequency spectrum analysis showed a marked change in the superimposed frequency curve only in animals fed on the high fat diet.     

The combined effect of high iron and zinc intake on copper status in rats

The interactions between copper, zinc, and iron intake in rats were investigated with regard to copper status. Weanling male rats were fed purified diets containing two levels of each of the three elements in a 2³ factorial design. The added amounts of copper, zinc, and iron in the diets were 5, 12, and 35 mg/kg feed or were 10 times as high. After feeding on the experimental diets for 4 wk, the rats were killed and copper concentrations in plasma and organs measured. Plasma copper concentration was lowered by high zinc and iron intakes but this was seen only in the rats fed the normal-copper instead of the high-copper diets. In essence, the effects of zinc and iron were additive. Neither in rats fed the normal-copper diets nor in those fed the high-copper diets did extra iron or zinc intake alter copper concentrations in liver, spleen, kidney, and tibia.     

Response of liver antioxidant system to taurine in rats fed high fructose diet

Fructose-fed rats were more susceptible to peroxidative damage as measured by thiobarbituric acid reactive species. The concentrations of lipid peroxides, diene conjugates, lipofuscin and hydroperoxides were significantly higher. The levels of enzymic antioxidants such as vitamin C, vitamin E and glutathione and activities of antioxidant enzymes were significantly lower in fructose-fed rats. When these rats received taurine in drinking water, peroxidative damage was minimal in both plasma and liver. Taurine was effective in inducing the antioxidant potential in fructose-fed rats. Increased peroxidative damage in liver is likely to be associated with fructose dependent pathology, which could be reduced by taurine by enhancing the antioxidant potential.     

The longitudinal effect of inhibiting fatty acid oxidation in diabetic rats fed a high fat diet.

This study was designed to examine the time-course of response to inhibition of fatty acid (FA) oxidation in rats rendered mildly diabetic with streptozotocin and fed a high fat diet (50% of energy derived from fat). Etomoxir, a specific carnitine palmitoyltransferase (CPT-1) inhibitor, was administered subcutaneously (12.5 mg/kg) to inhibit long chain fatty acid oxidation. Diabetic and non-diabetic control rats were maintained on the high fat diet. Following an overnight fast, glucose, free fatty acid (FFA) and triglyceride (TG) concentrations were determined after three days, one week and four weeks of treatment. The effect of Etomoxir treatment in reducing fasting glucose concentrations was not evident until after one week, while fasting FFA and TG concentrations were already reduced after three days treatment. All of these changes were maintained over the four week period (P less than 0.001), resulting in reduced levels of fasting plasma glucose (17.6 +/- 2.4 vs 22.3 +/- 1.9 mmol/l), fasting plasma TG (0.32 +/- 0.07 vs 0.98 +/- 0.14 mmol/l) and fasting serum FFA (1.52 +/- 0.26 vs 3.51 +/- 0.69 mEq/l). In addition, the improvements in glucose and lipid levels were accompanied by restored rates of growth towards that of non-diabetic control rats. These results suggest that the short term inhibition of FA oxidation improves fasting glucose, FFA and TG concentrations in diabetic rats fed a high fat diet.