Metabolic and hormonal investigations in long-term streptozotocin diabetic rats on different dietary regimens

Summary Groups of diabetic rats (65 mg/kg streptozotocin SC) were fed ad lib on three different dietary regimens for 43 weeks: a standard control diet (68% of calories as carbohydrate, 20% as protein, and 12% as fat), a low carbohydrate high protein diet (6% carbohydrate, 63% protein, 31% fat) or a low carbohydrate-high fat diet (5% carbohydrate, 75% fat, 20% protein). The high fat diet resulted in a fall of blood glucose from 700 to 350 mg/100 ml. Rats fed the high protein diet showed a similar initial decrease in blood glucose concentration, and a further improvement was evident from the 28th week on. After 43 weeks blood glucose levels were below 180 mg/100 ml and glycosuria below 100 mg/24 h in all rats fed the high protein diet. When rats exhibiting blood glucose levels below 180 mg/dl were transferred temporarily to standard diet blood glucose levels increased and marked glycosuria was observed. Rats on the standard diet maintained blood glucose concentrations greater than 500 mg/100 ml and glycosuria of about 16 g/24 h throughout the experiment. The pancreatic insulin content at death of rats fed the standard diet or the high fat diet was 1% of normal rats, whereas the values for the rats on the high protein diet were increased to 9%. Animals fed the low carbohydrate diets showed greater weight gain. In the high fat diet group there was a marked rise after 43 weeks in plasma triglycerides, free fatty acids, 3-hydroxybutyrate and acetoacetate in the plasma. Urea excretion was raised in the animals on the high protein diet. Thus, treatment with low carbohydrate diets for 10 months regardless of fat and protein content markedly improved the diabetic state of rats.     

Effects of diet and metoprolol on lipid levels in the blood plasma and morphology of the heart and intramural branches of coronary arteries of spontaneously hypertensive male rats. A 9-month study

Semipurified diets containing 0.5% cholesterol were used in a 9-month study with spontaneously hypertensive male rats to characterize the effects of the protein source (casein vs. soybean protein), and the selective beta 1-adrenoceptor antagonist metoprolol on both lipid levels in blood plasma and the aorta, and on the morphology of intramural branches of coronary arteries. Raised blood lipid levels were observed in these rats. A significant decline in HDL2 cholesterol took place, while plasma cholesterol belonging to lipoprotein fractions of lower density increased. Metoprolol treatment led to a substantial elevation of the plasma triacylglycerol level and, with time, a reduced cholesterolemic response. The use of soybean protein instead of casein had a persistent plasma lipid-lowering effect. Arteriosclerotic changes in the form of musculo-elastic thickenings, intimal cushions and homogeneous hyalin deposits appeared in the intramural coronary arteries of rats in all groups after 9 months on the diet. However, intimal deposition of lipid was only present in rats belonging to the casein group not treated with metoprolol. Rats of this group also showed more severe myocardial lesions in the form of scar tissue with or without inflammatory cell reaction.     

Melatonin effect on plasma adiponectin,leptin, insulin,glucose, triglycerides and cholesterol in normal and high fat–fed rats

Abstract: Melatonin effect on body weight progression, mean levels and 24‐hr pattern of circulating adiponectin, leptin, insulin, glucose, triglycerides and cholesterol were examined in rats fed a normal or a high‐fat diet. In experiment 1, rats fed a normal diet were divided into two groups: receiving melatonin (25 μg/mL drinking water) or vehicle for 9 wk. In experiment 2, animals were divided into three groups: two fed with a high‐fat diet (35% fat) and melatonin (25 μg/mL) or vehicle in drinking water for 11 wk, while a third group was given a normal diet (4% fat). At the end of experiments, groups of eight rats were killed at six different time intervals throughout a 24‐ hr period. Melatonin administration for 9 wk decreased body weight gain from the 3rd wk on without affecting food intake. A significant reduction in circulating insulin, glucose and triglyceride mean levels and disrupted daily patterns of plasma adiponectin, leptin and insulin were observed after melatonin. In high fat–fed rats, melatonin attenuated body weight increase, hyperglycemia and hyperinsulinemia, as well as the increase in mean plasma adiponectin, leptin, triglycerides and cholesterol levels. The high‐fat diet disrupted normal 24‐ hr patterns of circulating adiponectin, insulin and cholesterol, the effects on insulin and cholesterol being counteracted by melatonin. Nocturnal plasma melatonin concentration in control and obese rats receiving melatonin for 11 wk attained values 21–24‐fold greater than controls. The results indicate that melatonin counteracts some of the disrupting effects of diet‐induced obesity in rats.     

Atherosclerosis in rabbits identified as high and low responders to an atherogenic diet and the effect of treatment with a beta 1-blocker

In order to investigate whether initial plasma lipid concentrations could be used to distinguish between high and low responders to an atherogenic diet, rabbits were divided into 3 groups according to their plasma concentrations of cholesterol and phospholipids after 4 weeks on a standard rabbit diet. Plasma cholesterol and phospholipid levels were less than 0.5 mM, less than 1.1 mM, respectively, in group 1 (n = 17), greater than 0.5 mM, less than 1.1 mM, in group 2 (n = 13), and greater than 0.5 mM, greater than or equal to 1.1 mM, in group 3 (n = 14). After 7 weeks on a diet containing 0.25% cholesterol and 3% coconut oil, animals in groups 1 and 2 had a lower increase in their plasma lipid levels compared with group 3. Half of each group was then treated with the beta 1-adrenoceptor antagonist metoprolol during the next 14 weeks on the atherogenic diet. At the end of the study, the extent of atherosclerosis both in the aortas and in the coronary arteries of the control animals showed a positive correlation to plasma cholesterol and to plasma phospholipid concentrations integrated over time. The metoprolol-treated animals in groups 1 and 2 had a reduction of atherosclerosis compared with their respective controls. We conclude that subpopulations of rabbits that react differently on an atherogenic diet can be identified by their initial plasma lipid levels, and that metoprolol treatment of low responders to an atherogenic diet significantly reduces atherosclerotic lesions of the aorta.     

Effects of long-term treatment with metoprolol and hydrochlorothiazide on plasma lipids and lipoproteins

Abstract. In order to evaluate the effects of one-year antihypertensive treatment on plasma lipids and lipoproteins, 65 patients whose diastolic blood pressure was in the range 95-120 mmHg were randomly allocated to groups that received either hydrochlorothiazide or metoprolol, or both drugs when the response to one of them was insufficient to control blood pressure. Blood pressure was effectively reduced in all groups. Patients on hydrochlorothiazide showed a significant increase (P < 0.01) in low-density lipoprotein cholesterol (LDL-C) after 3 months of treatment. A significant increase in triglycerides was observed after 6 and 12 months, together with a decrease in high-density lipoprotein cholesterol (HDL-C) after 12 months (P < 0.05) of treatment in patients on metoprolol. In patients treated with both hydrochlorothiazide and metoprolol, total cholesterol increased after 3 (P < 0.001) and 6 months (P < 0.05), triglycerides increased after 6 (P < 0.01) and 12 months (P< 0.01), and LDL-C increased after 3 (P< 0.05), 6 (P < 0.001) and 12 months (P < 0.01) of treatment, respectively. In 61% of the patients, three or more lipid parameters were affected during the study period. We conclude that long-term antihypertensive treatment with hydrochlorothiazide, metoprolol, and particularly with both drugs, can induce lipid effects that deserve recognition, because in some cases these might counteract the possible benefit of a reduction in blood pressure on the prevention of coronary heart disease.     

A high-cholesterol, n-3 polyunsaturated fatty acid diet causes different responses in rats and hamsters

This study was designed to investigate the response to a high-cholesterol, n-3 polyunsaturated fatty acid (PUFA) or n-6 PUFA diet in rats and hamsters. Animals were fed n-3 or n-6 PUFA with a cholesterol-free diet, or with a diet enriched with cholesterol (0.5%, w/w) for 2 weeks. In rats and hamsters fed a cholesterol-free diet, plasma cholesterol, triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels in n-3 PUFA group were significantly lower than those in n-6 PUFA group. In contrast, when diets were supplemented with 0.5% cholesterol, the plasma cholesterol- and triglyceride-lowering effect of dietary n-3 PUFA disappeared. In hamsters fed with the atherogenic diet (0.5% dietary cholesterol) for 2 weeks, n-3 PUFA induced hypercholesterolemia more than n-6 PUFA, the increase being in the VLDL and low-density lipoprotein (LDL) fractions. Our data thus indicate that elevation of VLDL- and LDL-cholesterol in hamsters by n-3 PUFA, compared with n-6 PUFA, is dependent on 0.5% dietary cholesterol supplementation. In rats, on the other hand, dietary n-3 PUFA did not induce hypercholesterolemia more than n-6 PUFA when 0.5% cholesterol was supplemented. Although the effects of n-3 PUFA on plasma cholesterol, triglycerides and VLDL-triglycerides were similar in hamsters and rats, the interactive effects of n-3 PUFA and cholesterol on plasma and lipoprotein cholesterol levels differed in the two species. It was also found that plasma triglycerides, cholesterol and lipoprotein cholesterol levels in hamsters are higher than in rats in the presence and absence of dietary cholesterol. In addition, cholesterol feeding induces hypertriglyceridemia and hypercholesterolemia only in hamsters. Moreover, liver triglyceride concentrations increased in rats fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed rats were significantly lower than those in the n-6 PUFA-fed rats in the presence and absence of dietary cholesterol. However, triglycerides did not accumulate in the liver in hamsters fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed hamsters were not significantly different from those in the n-6 PUFA-fed hamsters in the presence and absence of dietary cholesterol. Therefore, these studies confirm marked species differences in response to the interactive effects of dietary n-3 PUFA and cholesterol.     

Food restriction in female Wistar rats. III. Thermotropic transition of membrane lipid and 5'-nucleotidase activity in hepatocytes

The effect of diet restriction was measured on the anisotropy parameter of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 5'-nucleotidase enzyme activity in liver plasma membrane preparates. Diet restriction was applied to rats 3.5 months old on an every-other-day schedule (EOD) and the rats were killed at the age of 28-29 months. Six months and 24 months rats, fed ad libitum (AL), were used as controls. The Arrhenius plots of anisotropy parameter of liver membranes from young, old AL and old EOD animals exhibited well defined breakpoints at 16.3 degrees C, 19.5 degrees C and 16.7 degrees C, respectively. The breakpoint temperature of 5'-nucleotidase activity was lower in samples from young rats as compared to those from old AL rats, whereas no difference was observed comparing young and EOD fed rats. Present results support the hypothesis that diet restriction modifies lipid composition of liver plasma membranes in such a way that the appearance of age-dependent alterations is delayed.     

Effects of dietary fatty acids on lipid metabolism in streptozotocin-induced diabetic rats

We measured the activity of liver delta9- and delta6-desaturases and examined plasma and liver microsome phospholipid fatty acid composition in control and diabetic rats fed a basal diet supplemented with 5% (by weight) olive oil (OO), sunflower oil (SO), or fish oil (FO), respectively. Plasma glucose, cholesterol, triacylglyceride, and phospholipid levels were also measured. An increase in plasma and liver microsome oleic acid and a decrease in arachidonic acid were found in diabetes. In the liver, docosahexaenoic acid levels were higher in diabetic versus control rats. Diabetes increased liver delta9-desaturase in OO-fed rats and did not modify delta6-desaturase activity in OO- or SO-fed rats. Both enzymatic activities were decreased in diabetic rats fed the FO diet. As a main conclusion, it appears that diet-induced alterations in membrane composition provide a mechanism for improving the diabetic condition in animals and overcoming the effect of insulin deficiency on desaturase activities. Plasma cholesterol was not modified either by diabetes or by diet. In diabetes, OO-fed rats showed the lowest levels of triglycerides. Plasma phospholipids were significantly higher in OO-fed versus FO-fed rats. These findings suggest that OO contributes to a better control of the hypertriglyceridemia accompanying diabetes as compared with the other two diets in this rat model.     

Effect of lifelong coenzyme Q10 supplementation on age-related oxidative stress and mitochondrial function in liver and skeletal muscle of rats fed on a polyunsaturated fatty acid (PUFA)-rich diet

This study investigates aging-related changes in lipid peroxidation and functionality in liver and skeletal-muscle mitochondria in rats fed a diet rich in polyunsaturated fatty acids (PUFA), depending on supplementation or not with coenzyme Q(10) (CoQ(10)). Two groups of rats were fed for 24 months on a PUFA-rich diet, differing in supplementation or not with CoQ(10). At 6 and 24 months mitochondria were analyzed for fatty acid profile; hydroperoxides; alpha-tocopherol; CoQ(9;) CoQ(10;) cytochromes b, c+c(1), and a+a(3) contents; cytochrome c oxidase activity; and catalase activity in cytosol. Results of this study showed for the supplemented group an age-associated decrease in the peroxidizability index, an increase in catalase activity in skeletal muscle, and modulation of the aging-related changes in different mitochondrial electron-transport-chain components in skeletal muscle. These findings provide mechanisms to explain the effect of CoQ(10) in extending the life span of animals fed a PUFA-rich diet.     

Membrane microviscosity, blood pressure and cytosolic pH in Dahl rats: the influence of plasma lipids.

OBJECTIVE: To determine the relationships between blood pressure, membrane microviscosity, plasma lipids and cytosolic pH in Dahl rats susceptible or resistant to salt hypertension. DESIGN AND METHODS: Blood pressure, plasma triglycerides and total cholesterol, platelet cytosolic pH (pHi) and the microviscosity of both outer membrane leaflet (TMA-DPH fluorescence anisotropy) and membrane lipid core (DPH fluorescence anisotropy) were studied in platelets and erythrocyte ghosts of Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats fed either a low-salt diet (0.3% NaCl) until the age of 9, 15 or 24 weeks or a high-salt diet (4% NaCl) for 5 or 10 weeks after weaning. RESULTS: At low salt intake, DPH but not TMA-DPH anisotropy increased with age in platelets of SS/Jr rats. Chronic high salt intake was accompanied by an increase of DPH anisotropy in platelets but not in erythrocyte ghosts of SS/Jr rats. Platelet DPH anisotropy correlated positively with blood pressure of salt-loaded SS/Jr rats. Chronic high salt intake also reduced pHi in platelets, the regulation of which seemed to be related to the changes in TMA-DPH anisotropy. This especially concerns the thrombin-induced pHi rise which was inversely related to basal pHi, plasma lipids and TMA-DPH anisotropy. Altered membrane lipid composition might be the underlying mechanism because both membrane microviscosity and platelet pHi regulation were reported to correlate significantly with plasma triglycerides and/or cholesterol. CONCLUSIONS: Platelets of salt hypertensive Dahl rats are characterized by an increased microviscosity of membrane lipid core which correlated positively with blood pressure. The major influence of plasma triglycerides on DPH anisotropy should be taken into consideration when investigating the links between membrane microviscosity and blood pressure. On the other hand, the changes in microviscosity of the outer membrane leaflet might be involved in pHi regulation (probably through control of the Na+/H+ exchanger).     

Long-term effects of high dietary fiber intake on glucose tolerance and lipid metabolism in GK rats: comparison among barley, rice, and cornstarch

Whether the intake of high dietary fiber may improve glycemic control in individuals with type 2 diabetes has been controversial. This study was conducted to observe the long-term effects of dietary fiber intake on glucose tolerance and lipid metabolism in rats. Thirty male type 2 diabetic model GK rats were divided randomly into 3 groups. Each group was fed either a barley (high-dietary fiber) diet, rice (low-dietary fiber) diet, or cornstarch (very-low-dietary fiber) diet. The rats were pair-fed for 9 months. The intake of the barley diet significantly improved the area under the plasma glucose concentration time curves, lowered the fasting plasma glucose and glycosylated hemoglobin levels, and decreased plasma total cholesterol (T Chol), triglycerides (TG), and free fatty acid (FFA) levels. This study demonstrated that long-term intake of barley has beneficial effects on glucose tolerance and lipid metabolism and suggests the intake of unrefined cereal foods should increase as a diet therapy for type 2 diabetes.     

Increased plasma immunoreactive endothelin-1 concentration in hypercholesterolemic rats.

This study examined the influence of hypercholesterolemia on the concentration of plasma immunoreactive (ir) endothelin-1 in rats. Plasma ir-endothelin-1, total cholesterol, triglycerides, and lipoprotein fraction concentrations were measured in three groups of rats; ie, fed a standard diet, a high cholesterol diet, or a high cholesterol diet supplemented with the antihypercholesterolemic drug clinofibrate for 4 and 8 weeks. In the rats fed cholesterol for 8 weeks, morphological changes in thoracic and abdominal aortas were examined. Plasma total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL) and ir-endothelin-1 concentrations increased significantly in the cholesterol-fed rats after both 4 and 8 weeks. In the clinofibrate-treated rats, these lipid parameters and plasma ir-endothelin-1 levels after 4 and 8 weeks were significantly lower than in the cholesterol-fed rats. The plasma ir-endothelin-1 concentration was correlated with plasma total cholesterol, LDL, and VLDL concentrations in the three study groups after 4 and 8 weeks. Morphologically, neither foam cells formation nor intimal thickening was observed in rats fed the high cholesterol diet for 8 weeks. These observations indicate that hypercholesterolemia without atherosclerosis elevates the plasma ir-endothelin-1 level in rats. The observed increase in plasma ir-endothelin-1 associated with hypercholesterolemia may play a role in the initiation or development of atherosclerotic vascular lesions.     

Effect of chronic ethanol consumption on the pancreas of the hamster

The purpose of this study was to determine the effect of chronic ethanol consumption on pancreatic morphology and biochemistry in the hamster, with special attention to lipid changes. A control group of Syrian golden hamsters fed a synthetic liquid diet was compared to an ethanol group pair-fed the same diet with ethanol substituted for 35% of the carbohydrate calories. The animals were sacrificed at 7 weeks and 3, 6, 9, and 12 months. After 12 months of ethanol consumption, a significant decrease in pancreatic triglycerides and a significant increase in pancreatic RNA was seen. These changes were associated with a rise in pancreatic weight and protein content in the ethanol group, reversing a six-month decline in these values. This rise in RNA and protein in the ethanol-treated group corresponded with the appearance of large abnormal zymogen granules. Other ultrastructural features such as lipid droplets, mitochondria, and endoplasmic reticulum were not altered by ethanol. Ethanol did increase the water content of the pancreas. Although ethanol had no effect on the fasting levels of insulin or pancreatic polypeptide, the fasting serum gastrin immunoreactivity was significantly lower in the ethanol animals. This study shows that chronic ethanol consumption produces a metabolic change in the hamster by 12 months which is suggestive of increased protein synthesis with a decrease in pancreatic triglycerides and no lipid droplet formation.This study was supported by the Medical Research Service of the Veterans Administration Medical Center.     

The effect of age and diet on the cellular protein synthesis of liver of male mice

The rates of cellular protein synthesis were estimated in liver by determining: 1) the half lives of proteins by the rate of disappearance of radioactivity following the intraperitoneal injection of C¹⁴ labeled sodium bicarbonate, and 2) the cellular protein levels estimated by the concentration of proteins and DNA of the tissue. The age studies were carded out on C57BL/6J mice, aged 12, 18, 24, and 32–34 months, fed the NIH Open Formula Mouse Diet. Dietary studies were carried out on 9 month old B₆D₂F₁ mice fed purified diets which contained crude casein. The animals were offered one of the following regimens. One group was fed a 24% protein diet ad libitum. Another group was fed a 4% protein diet ad libitum. The third and fourth groups were fed the 24% protein diet ad libitum for twenty-four hours on Monday and Wednesday, and for eight hours on Friday. The third group was sacrificed following a 24 hour feeding period, while the fourth group wee sacrificed following a 24 hour fasting period. The rates of disappearance of radioactivity from the liver proteins of mice were not statistically significantly affected by age or dietary regimens. However, there was a 27% progressive decrease in the cellular protein synthesis of liver between the ages of 12 and 32–34 months. Feeding a low protein diet ad libitum resulted in a 28% decrement. In addition, during the 24 hour period of starvation during intermittent feeding, there is a 30% decrease in cellular protein synthesis which returns to normal levels during the 24 hour feeding period.     

JTT-130, a novel intestine-specific inhibitor of microsomal triglyceride transfer protein, ameliorates impaired glucose and lipid metabolism in Zucker diabetic fatty rats

Aim: Microsomal triglyceride transfer protein (MTP) takes part in the mobilization of triglyceride‐rich lipoproteins from enterocytes and hepatocytes. We investigated the effects of JTT‐130, a novel intestine‐specific MTP inhibitor, on impaired glucose and lipid metabolism in Zucker diabetic fatty (ZDF) rats. Methods: Male ZDF rats were fed a regular powdered diet with or without JTT‐130 as a food admixture (0.01–0.02%) for 6 weeks. Food intake, body weight, blood biochemical parameters, fecal lipid contents, hepatic lipid contents, tissue mRNA levels and glucose utilization in adipose tissues were assessed. An intraperitoneal glucose tolerance test (IPGTT) and histological analysis of the pancreas were performed. Results: JTT‐130 treatment decreased food intake, glycated hemoglobin, plasma levels of glucose, triglycerides and total cholesterol, hepatic levels of triglycerides and cholesterol and hepatic mRNA levels of glucose‐6‐phosphatase, phosphoenolpyruvate carboxykinase and fructose‐1,6‐bisphosphatase. JTT‐130 treatment increased fecal levels of free fatty acids and cholesterol, plasma levels of glucagon‐like peptide‐1 and peptide YY, mRNA levels of glucose transporter 4 (GLUT4) and lipoprotein lipase in adipose tissues and GLUT4 in muscle and glucose utilization in adipose tissues. Plasma insulin decreased after 2 weeks and increased after 4 weeks of JTT‐130 treatment. Plasma glucose in the JTT‐130‐treated rats was lower with higher plasma insulin than in the control rats during the IPGTT. The islets of the JTT‐130‐treated rats were larger and contained more insulin than those of the control rats. Conclusions: JTT‐130 ameliorates impaired glucose and lipid metabolism in the ZDF rats thereby suggesting that JTT‐130 could be useful for prevention and treatment of type 2 diabetes.     

Fenofibrate lowers adiposity and corrects metabolic abnormalities, but only partially restores endothelial function in dietary obese rats

In humans, dietary-induced obesity markedly increases plasma lipid profile and impairs vascular function leading to increased incidence of cardiovascular events. We have recently reported that chronic withdrawal of obesity-inducing diet attenuates obesity and completely corrects endothelial function. The aim of this study was to investigate whether fenofibrate-induced decrease in adiposity would also correct vascular function in the presence of obesity-inducing diet. Wistar rats were fed with either standard laboratory chow (lean, n = 9) or given a highly palatable diet (diet-fed, n = 18) for 15 weeks. After 7 weeks, half of the diet-fed group was treated with fenofibrate (fenofibrate-treated, n = 9) for 8 weeks before being sacrificed. Untreated diet-fed (n = 9) rats had significantly higher body weight, total fat mass (by up to two-fold, p < 0.001 for both), and raised fasting plasma levels of insulin, leptin and triglycerides (up to 110%; p < 0.001), but not glucose or nonesterified fatty acids (NEFA) than both lean control and fenofibrate-treated groups. Resistance mesenteric arteries responses to KCl- and noradrenaline-induced vasoconstriction were similar in all three groups. However, compared with lean controls, endothelium-dependent vasorelaxation responses were shifted to the right in both untreated and fenofibrate-treated diet-fed groups. Fenofibrate treatment improved endothelium-dependent vasorelaxation at only high carbamycholine concentrations (10 microM). There were no differences in endothelium-independent vasorelaxation between the three groups. These results indicate that, in the presence of obesity-inducing diet, fenofibrate markedly reverses obesity and corrects insulin resistance and lipid profile, but it only has a limited beneficial effect on vascular function. Therefore, it seems that diet component rather than obesity per se plays a key role in the genesis of vascular abnormalities.     

Therapeutic effects of tender coconut water on oxidative stress in fructose fed insulin resistant hypertensive rats

ObjectiveTo investigate whether tender coconut water (TCW) mitigates oxidative stress in fructose fed hypertensive rats.MethodsMale Sprague Dawley rats were fed with fructose rich diet and treated with TCW (4 mL/100 g of body weight) for 3 subsequent weeks. Systolic blood pressure was measured every three days using the indirect tail cuff method. At the end of the experimental period, plasma glucose and insulin, serum triglycerides and free fatty acids, lipid peroxidation markers (MDA, hydroperoxides and conjugated dienes) and the activities of antioxidant enzymes were analyzed in all the groups.ResultsTreatment with TCW significantly lowered the systolic blood pressure and reduced serum triglycerides and free fatty acids. Plasma glucose and insulin levels and lipid peroxidation markers such as MDA, hydroperoxides and conjugated dienes were significantly reduced in fructose fed rats treated with TCW. Activities of antioxidant enzymes are up regulated significantly in TCW treated rats. Histopathological analysis of liver showed that TCW treatment reduced the lipid accumulation and inflammatory infiltration without any significant hepatocellular damage.ConclusionsThe overall results suggest that, TCW treatment could prevent and reverse high blood pressure induced by high fructose diet probably by inhibition of lipid peroxidation, upregulation of antioxidant status and improved insulin sensitivity.     

Serum cholesterol and lipid peroxidation are decreased by melatonin in diet-induced hypercholesterolemic rats

The purpose of this study was to investigate the effect of melatonin, at pharmacological doses, on serum lipids of rats fed with a hypercholesterolemic diet. Therefore, different groups of animals were fed with either the regular Sanders Chow diet or a diet enriched in cholesterol. Moreover, animals were treated with or without melatonin in the drinking water for 3 months. We show that melatonin treatment did not affect the levels of cholesterol or triglycerides in rats fed with a regular diet. However, the increase in total cholesterol and low-density lipoprotein (LDL)-cholesterol induced by a cholesterol-enriched diet was reduced significantly by melatonin administration. On the other hand, melatonin administration prevented the decrease in high-density lipoprotein (HDL)-cholesterol induced by the same diet. No differences in the levels of very low-density lipoprotein (VLDL)-cholesterol and triglycerides were found. We also found that melatonin administration slightly decreased serum uric, bilirubin and increased serum glucose levels. Other biochemical parameters, including total proteins, creatinine, urea, phosphorus, calcium, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyltranspeptidase (gamma-GT), acetyl cholinesterase (AcCho), and alkaline phosphatase (ALP) were not modified by melatonin treatment. Finally, lipid peroxidation (LPO) was studied in membranes of liver, brain, spleen, and heart as an index of membrane oxidative damage. Results show that hypercholesterolemic diet did not modify the LPO status in any of the tissues studied. However, chronic melatonin administration significantly decreased LPO. Results confirm that melatonin participates in the regulation of cholesterol metabolism and in the prevention of oxidative damage to membranes.     

Effect of prolonged ethanol intake on pancreatic lipids in the rat pancreas

Although fat accumulation in acinar cells is the earliest histopathological change in the pancreas of patients and experimental animals, there are few long-term studies regarding lipid composition of the pancreas in alcoholism. In the present study, female Sprague-Dawley rats were divided into three groups each fed Wayne Rodent-Blox ad libitum or Lieber-DeCarli diet with 36% of maltose dextrin calories replaced with ethanol ad libitum, or isocaloric amounts of liquid diet for a period of 21 months resulting in changes of chronic pancreatitis in ethanol-fed rats. A low level of triglycerides, a high level of cholesterol ester and moderately elevated phospholipids, low incorporation of [14C]palmitoyl in triglycerides, increased 14C activity in phospholipids, and cholesterol ester were found by thin-layer chromatography in ethanol-fed rats. These data indicate that the pancreas synthesized triglycerides and other lipid components in the same way as liver and fat cells. Chronic ethanol ingestion caused marked changes in pancreatic lipid metabolism due to altered enzyme activities involved in the lipid pathways.     

Influence of alpha-lipoic acid on lipid peroxidation and antioxidant defence system in blood of insulin-resistant rats

Background: High fructose feeding induces insulin resistance and hyperinsulinaemia in rats. A role for oxidative stress in the occurrence of insulin resistance has been suggested by several workers. Aim: The aim of this study was to investigate the effect of α‐lipoic acid (LA) on oxidant–antioxidant balance in rats fed on a high‐fructose diet that showed characteristic features of insulin resistance. Methods: Male Wistar rats weighing 150–170 g were divided into seven groups. The control group received the control diet containing starch. The fructose group was given a high‐fructose diet (>60% of total calories). The third and fourth groups were given fructose diet and were administered two different doses of LA at a low dose (35 mg/kg body weight) and high dose (70 mg/kg body weight) using olive oil as vehicle. The fifth group received fructose diet and olive oil. The sixth group received control diet and was administered LA (70 mg/kg body weight). And, the seventh group received the control diet and olive oil. Products of lipid peroxidation and activities of enzymic antioxidants, namely superoxide dismutase, catalase, glutathione peroxidase, glutathione‐S‐transferase and glutathione reductase, in red blood cells were assayed. Levels of non‐enzymic antioxidants α‐tocopherol, ascorbic acid and reduced glutathione were determined in plasma. Results: The levels of lipid peroxides, diene conjugates and thiobarbituric acid‐reactive substances were significantly higher in fructose‐fed rats. Inadequate antioxidant system was observed in high‐fructose‐fed rats. Treatment of fructose rats mitigated the imbalance between peroxidation and antioxidant defence system at both the doses tested. Increases in glucose, triglycerides, free fatty acids, insulin and insulin resistance were observed in fructose‐fed rats. LA administration prevented these alterations and improved insulin sensitivity. Significant positive correlations were obtained between insulin resistance and lipid peroxidation indices. Conclusions: Increased lipid peroxidation and deficient antioxidant system are observed in high‐fructose‐fed rats. LA administration preserves the antioxidant system and lowers lipid peroxidation. The findings suggest an interrelationship between lipid peroxidation and insulin resistance.