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.     

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.     

Hypolipidemic effect of methanolic extract of Dolichos biflorus Linn. in high fat diet fed rats

High fat diet fed rats showed significant increased levels of plasma and tissue total cholesterol, triglycerides, free fatty acids, phospholipids, plasma LDL cholesterol and decreased level of plasma HDL cholesterol. Methanolic extract of D. biflorus administration to high fat diet fed rats showed near to normal levels of the above lipids in plasma and tissues. Higher dose of the extract (400 mg/kg body weight) showed comparable results with standard drug atorvastatin. It is concluded that the methanolic extract of D. biflorus possesses hypolipidemic activity in high fat diet fed rats.     

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.     

Effect of capsaicin on skeletal muscle lipoprotein lipase in rats fed high fat diet

A synthetic analogue of capsaicin (0.2 mg%) fed to female Wistar rats along with a high fat diet for 11 weeks, lowered adipose tissue weight and also liver and serum triglycerides. The compound elevated total post heparin plasma lipase and skeletal muscle lipase activities. The increase in the latter indicates the possible mechanism by which capsaicin enhances serum triglyceride uptake by muscle tissue and in turn lowers triglyceride levels. A single dose of capsaicin even at a much higher level failed to lower serum triglycerides emphasizing the necessity of continuous ingestion of capsaicin for exerting its hypolipidemic effect.     

Occurrence of pancreatic ductal cell dysplasia in rats fed with a high fat diet and ethanol

The effects of alcohol and diet on acute pancreatitis were studied in 192 male Wistar rats. The animals were fed with standard laboratory food up to three months of age and, after that, were divided into four groups of 48 animals, each group receiving a different diet: standard, fat-rich, protein-rich or carbohydrate-rich. In each diet group, 24 animals obtained 15% (v/v) ethanol in their drinking solution while the other 24 rats had water ad libitum. The diet period lasted for 12 weeks, after which acute experimental pancreatitis was induced under diethyl ether anesthesia by ductal injection of rat bile into the pancreatic ducts. Moderate or severe ductal cell dysplasia developed in three of the 15 survivors in the group fed with a high-fat diet and 15% ethanol in their drinking solution. Mild acute pancreatitis was histologically found in 13 rats and moderate pancreatitis in one rat in this group. One rat did not show any pancreatic parenchymal changes. Two of the rats with ductal cell dysplasia had mild pancreatitis and the pancreas of the third rat was normal in this respect. Dysplastic changes were not found in any other experimental group used in the study. The observation is statistically significant at p less than 0.025 level. The results indicate that alcohol and a high fat diet together might have a carcinogenic effect on pancreatic ductal epithelium in rats.     

Antiatherogenic effects of cilostazol and probucol alone, and in combination in low density lipoprotein receptor-deficient mice fed with a high fat diet.

Cilostazol, an antiplatelet drug, and probucol, a cholesterol-lowering drug, are reported to ameliorate atherosclerosis in animal models. However, their combined effect on atherosclerosis is unclear. We therefore evaluated their combined effect on atherosclerotic lesions in LDL receptor-deficient mice. Male LDL receptor-deficient mice were fed a high fat diet with or without cilostazol alone, probucol alone, or with cilostazol and probucol in combination, for 8 weeks. Body weight and plasma lipid levels were measured before and during treatment. At the end of treatment, the size distribution of plasma lipoproteins was analyzed by HPLC and then plasma HDL cholesterol levels and en face aortic atherosclerotic lesion areas were measured. Probucol alone significantly decreased both total cholesterol and HDL cholesterol, while cilostazol alone did not decrease total cholesterol, but significantly increased HDL cholesterol. Both cilostazol alone and probucol alone significantly decreased atherosclerotic lesion areas, and their combined administration showed more significant decreases than when each drug was administered singly. The combination of cilostazol and probucol was more effective in preventing atherosclerotic lesion formation than the administration of each drug alone; this may provide us with a new strategy for treating atherosclerosis.     

Regulation of hepatic very-low-density lipoprotein secretion in rats fed on a diet high in unsaturated fat.

Rats were fed ad libitum on either a standard, high-carbohydrate, chow diet or a similar diet supplemented with 15% unsaturated fat (corn oil). Hepatocytes were prepared either during the dark phase (D6-hepatocytes) or during the light phase (L2-hepatocytes) of the diurnal cycle. In hepatocytes from rats fed on the unsaturated-fat-containing diet, secretion of very-low-density lipoprotein (VLDL) triacylglycerol was inhibited to a greater extent in the D6- than in the L2-hepatocytes. Plasma non-esterified fatty acid concentrations were elevated to the same extent at both D6 and L2 in the unsaturated-fat-fed animals. The secretion of VLDL esterified and non-esterified cholesterol was relatively insensitive to changes in the unsaturated-fat content of the diet. This resulted in proportionate increases in the content of these lipid constituents compared with that of triacylglycerol in the nascent VLDL. There was also an increase in the ratio of esterified to non-esterified cholesterol in the nascent VLDL produced by hepatocytes of the unsaturated-fat-fed animals. In the D6-hepatocytes from the unsaturated-fat-fed animals, the decrease in the secretion of VLDL triacylglycerol could not be reversed by addition of exogenous oleate (0.7 mM) to the incubation medium. In contrast, addition of a mixture of lactate (10 mM) and pyruvate (1 mM) stimulated both fatty acid synthesis de novo and the rate of VLDL triacylglycerol secretion. Secretion of esterified and non-esterified cholesterol also increased under these conditions. Insulin suppressed the secretion of VLDL triacylglycerol and cholesteryl ester under a wide range of conditions in all types of hepatocyte preparations. Non-esterified cholesterol secretion was unaffected. In hepatocytes prepared from the fat-fed animals, these effects of insulin were more pronounced at D6 than at L2. Glucagon also inhibited VLDL lipid secretion in all types of hepatocyte preparations. The decrease in cholesterol secretion was due equally to decreases in the rates of secretion of both esterified and non-esterified cholesterol.     

The effect of taurine on cholesterol degradation in mice fed a high-cholesterol diet

The hypocholesterolemic effect of taurine was examined in mice fed a high-cholesterol diet containing 1% cholesterol and 0.25% sodium cholate. Male C57BL/6 mice were divided into 3 groups: control group (HC), 1% taurine-supplemented group (HCT+), and taurine-deficient group (HCT-) produced by supplying 0.5% guanidinoethyl sulfonate (GES) solution ad libitum instead of water. After they were fed with the respective diet or drinking water for 4 weeks, the liver taurine level was reduced 80% in the HCT- group compared with that in the HC group, although there was no difference in the serum taurine amount between the two groups. The formation ratio of cholesterol gallstones increased from 71% to 100% by taurine deficiency, and decreased to 0% by taurine supplementation. Compared with the HC group, serum and liver cholesterol significantly decreased, and the excretion of fecal bile acid notably rose in the HCT+ group but tended to lower in the HCT- group. There were no differences in LDL receptor protein level among the three groups. In the subsequent experiment, triglycerides (TG) secretion rate was determined and found to be significantly suppressed by taurine supplementation. In conclusion, it is suggested that taurine does not up-regulate LDL receptor protein level, and the decrease in cholesterol in the circulation is mainly due to its suppressive effect on TG secretion from the liver.     

Gender-dependent gene expressions in brown adipose tissue of lean and obese rats fed a high fat diet

In the present study, we identified the interscapular brown adipose tissue (BAT) genes showing differential expression using DNA microarray analysis in order to better understand a gender-difference in gene regulation, as well as molecular abnormalities in dietinduced obesity. To understand the detailed changes in the gene expression profiles in BAT caused by HFD feeding, we extracted and summarized the genes that were up- or down-regulated by more than 1.5-fold between the genders. In this analysis, significant global changes were observed at the mRNA levels between the genders, as well as lean and obese rat BAT rendered by a HFD. Herein, we report for the first time that a series of genes, which might be involved in fatty acid oxidation and thermogenic regulation, were more highly expressed in females than in males. These results allowed us to conclude that compared to males, females have greater fat clearing capacity through the activation of genes encoding enzymes of fat oxidation. In addition, we found that females have higher thermogenic capacity due to increased expressions of genes involved in energy expenditure. In conclusion, the microarray data of gender dimorphism in BAT will prove valuable in improving gender awareness in the health care system and for the development of evidence-based gender specific clinical recommendations.     

Effect of chemically different calcium antagonists on lipid profile in rats fed on a high fat diet.

Different classes of calcium antagonists, viz. verapamil (diphenylalkylamine), diltiazem (benzothiazepine), nifedipine, felodipine and nimodipine (dihydropyridines), were examined for their effects on lipid profile in rats. Clofibrate was the reference standard. Clofibrate significantly prevented the rise of serum triglycerides and total cholesterol produced by high fat diet and raised antiatherogenic index to 1.6 times than that of high fat diet controls. Of the calcium antagonists studied, felodipine was most effective in preventing the rise of serum triglycerides and total cholesterol in high fat diet fed rats. Felodipine's antiatherogenic index was very high (886%)--much more than that of clofibrate (303%). Diltiazem and nimodipine which also significantly prevented the rise in triglycerides and total cholesterol produced by high fat diet had a moderately beneficial antiatherogenic index similar to that of clofibrate. Though verapamil and nifedipine slightly increased the triglyceride levels, total cholesterol levels were reduced only by verapamil and not by nifedipine. Despite this both these drugs moderately raised antiatherogenic index similar to clofibrate.     

Hypolipidemic and antioxidant activities of Sanchi (Radix Notoginseng) in rats fed with a high fat diet

Sanchi, also known as Radix Notoginseng, is a Chinese traditional medicine prepared from roots of the herb Panax notoginseng. Sanchi is traditionally used as a hemostatic to control internal and external bleeding but also shows diverse bioactivities that include increasing coronary blood flow and reducing myocardial oxygen consumption and blood pressure. Although research into the potential cardioprotective effects of Sanchi is ongoing in the field of traditional Chinese medicine, we sought to explore potential benefits in cardiovascular disorders associated with excess cholesterol and hyperlipidemia. We have investigated the effects of Sanchi as a dietary supplement on hyperlipidemia and oxidative stress in male Sprague-Dawley rats maintained on a high-fat diet. Diets were supplemented with Sanchi at 0.25%, 0.5% and 1% (w/w) for four weeks, while control animals received no supplement. Sanchi administration to hyperlipidemic rats resulted in a significant decline in serum levels of total cholesterol, triglycerides and low density lipoprotein-cholesterol, with an increase in serum high-density lipoprotein-cholesterol levels. Treated animals also showed reduced levels of hepatic HMG-CoA reductase. Furthermore, Sanchi improved hepatic antioxidant status as assessed by superoxide dismutase and glutathione peroxidase activities and reduced levels of lipid peroxidation. These results suggest that Sanchi consumption can improve lipid profiles, inhibit peroxidation, and increase the activity of antioxidant enzymes, and is thereby likely to reduce the risk of coronary heart disease associated with hyperlipidemia and oxidative stress.     

Effect of non-digestible gluco-oligosaccharides on glucose sensitivity in high fat diet fed mice

Non digestible dietary carbohydrates have been reported to modify lipaemia and post-prandial glycaemia and insulinaemia. The aim of this study was to investigate the effect of a non-digestible gluco-oligosaccharides (GOS) diet on glucose, insulin, triglycerides and free fatty acid blood levels and glucose sensitivity in high fat diet fed mice (a high fat diet composed of 45% fat, 35% carbohydrate and 20% protein). Female C57B16/J mice were divided into two groups fed a high fat diet (HF) for 20 weeks supplemented or not with 1.5 g/kg/day of GOS (HF-GOS). The GOS supplementation did not change body weight nor fat pad mass, nor any of the blood parameters measured (glucose, insulin, leptin, triglycerides, and free fatty acids). However, mice which received the GOS supplemented diet showed an increased glucose utilization after a 1 g/kg load of glucose compared with the mice fed the high fat diet alone. Our results suggest a role for non-digestible GOS in the regulation of carbohydrate metabolism.     

Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet

High fat diet (HFD) is a common cause of metabolic syndrome and type 2 diabetes mellitus. Published data showed that HFD and subsequent dyslipidemia are major triggers for oxidative stress. Forty-eight male Sprague–Dawley rats, weighing 170–200 g, were divided into six groups: control, control with vitamin E (100 mg/kg/day, i.p.), control with simvastatin (SIM) (10 mg/kg of body weight/day), HFD, HFD with vitamin E, and HFD with SIM. Standard and high cholesterol diets were given for 15 weeks and SIM and vitamin E were added in the last 4 weeks. In all rats, serum vitamin E, total cholesterol (TC), triglycerides (TG), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) as well as cardiac and hepatic thiobarbituric acid-reactive substances (TBARS) and antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) were measured. Also, electrocardiogram (ECG) was recorded. HFD significantly increased QTc interval, heart rate (HR), serum TC, TG, LDL, ALT, AST, ALP, GGT, liver TG, and cardiac and hepatic TBARS but decreased antioxidants and HDL, while SIM decreased HR, liver TG, serum TC, TG, and LDL and increased HDL in HFD rats. Vitamin E had no effect. Moreover, SIM and vitamin E decreased QTc interval, serum ALT, AST, ALP, GGT, and cardiac and hepatic TBARS and increased antioxidants in HFD rats. Histopathological observations confirm the biochemical parameters. SIM and vitamin E slow progression of hypercholesterolemia-induced oxidative stress in liver and heart and improve their functions.     

Effect of short-term exercise training on muscle glycogen in resting conditions in rats fed a high fat diet.

It has been reported that exercise training increases muscle glycogen storage in rats fed a high carbohydrate (CHO) diet in resting conditions. The purpose of this study was to examine whether a 3-week swimming training programme would increase muscle glycogen stores in rats fed a high-fat (FAT) diet in resting conditions. Rats were fed either the FAT or CHO diet for 7 days ad libitum, and then were fed regularly twice a day (between 0800 and 0830 hours and 1800 and 1830 hours) for 32 days. During this period of regular feeding, half of the rats in both dietary groups had swimming training for 3 weeks and the other half were sedentary. The rats were not exercised for 48 h before sacrifice. All rats were killed 2 h after their final meal (2030 hours). The glycogen contents in red gastrocnemius muscle, heart and liver were significantly higher in sedentary rats fed the CHO diet than in those fed the FAT diet. Exercise training clearly increased glycogen content in soleus, red gastrocnemius and heart muscle in rats fed the CHO diet. In rats fed the FAT diet, however, training did not increase glycogen content in these muscles or the heart. Exercise training resulted in an 87% increase of total glycogen synthase activity in the gastrocnemius muscle of rats fed the CHO diet. However, this was not observed in rats fed the FAT diet. The total glycogen phosphorylase activity in the gastrocnemius muscle of the rats of both dietary groups was increased approximately twofold by training.(ABSTRACT TRUNCATED AT 250 WORDS)