Lipid Metabolism In Wistar Rats Research Articles

A novel compounded cyproheptadine hydrochloride oral solution: Accelerated stability study and effects on glucose and lipid metabolism in Wistar rats

The present study developed a compounded oral solution (COS) containing an active component cyproheptadine hydrochloride (CY) in association with pharmaceutical adjuvants. The main objective is to demonstrate the stability of this solution and the in vivo effects on serum and liver parameters of glucose and lipid metabolism. After 180 days of analysis the COS showed physicochemical stability (pH and specific gravity) when submitted to different temperatures (24 °C and 40 °C), but the chemical stability, presented by the content of CY (%) in the formulation, showed that the degradation rate of CY increased 20x when submitted to a stress condition (40 °C). Male Wistar rats were treated with IOS 1.5 (industrial oral solution 1.5 mg.kg-1) or saline for 21 days and IOS 5.0 or COS (5 mg.kg-1) or placebo by gavage for 23 days. Treatment with IOS 1.5 increased liver cholesterol by 30 % without changing liver and body weight in this group. In contrast, treatment with IOS and COS (5 mg.kg-1) increased final body weight by 8 % compared to placebo. Interestingly, the COS group had increased liver glycogen accompanied by reduced food intake compared to IOS. However, COS and IOS 5.0 did not induce changes in adipose tissue weight, liver weight, as well as serum glucose, triacylglycerol and cholesterol levels. This work provides us with data that prove the stability of the compound solution at room temperature, as well as inducing an increase in the final body weight of rats with no alteration in glucose and lipid metabolism.

Effect of chain length and saturation of the fatty acids in dietary triglycerides on lipid metabolism in Wistar rats.

We investigated the effect of the chain length and the degree of saturation of fatty acids in dietary triglycerides on serum lipid profiles and hepatic lipid metabolism in Wistar rats. Fat component of the basal diet (soybean oil) was replaced with fats with fatty acids of different chain lengths and saturation and the serum lipids were monitored for 150days. Principal component (PC) analysis of serum lipid components was related to chain length and saturation. The combined effect of chain length and saturation on PC 1 scores was evaluated by multiple regression analysis. The results indicated that average chain length of the fatty acids of triglycerides has a higher influence on the quality of serum lipid parameters than the average degree of saturation. Expression of selected genes responsible for lipid metabolism showed similar trends in medium chain saturated and long chain polyunsaturated diet groups. PRACTICAL APPLICATIONS: Dietary lipids contain a wide range of saturated and unsaturated fatty acids with different chain lengths. Overall contribution of these different fatty acids decides the health effects of the lipids in the diet. Present study shows that the fats with medium chains and higher degree of saturation and fats with long chains and higher degree of unsaturation (lower degree of saturation) affect serum lipid parameters and expression of hepatic genes involved in the lipid metabolism in a similar manner. Such information is important for physicians to plan dietary schemes to improve the nutritional health and manage the noncommunicable diseases.

Beneficiary effect of Commiphora mukul ethanolic extract against high fructose diet induced abnormalities in carbohydrate and lipid metabolism in wistar rats

The present study was proposed to elucidate the effect of Commiphora mukul gum resin elthanolic extract treatment on alterations in carbohydrate and lipid metabolisms in rats fed with high-fructose diet. Male Wistar rats were divided into four groups: two of these groups (group C and C+CM) were fed with standard pellet diet and the other two groups (group F and F+CM) were fed with high fructose (66 %) diet. C. mukul suspension in 5% Tween-80 in distilled water (200 mg/kg body weight/day) was administered orally to group C+CM and group F+CM. At the end of 60-day experimental period, biochemical parameters related to carbohydrate and lipid metabolisms were assayed. C. mukul treatment completely prevented the fructose-induced increased body weight, hyperglycemia, and hypertriglyceridemia. Hyperinsulinemia and insulin resistance observed in group F decreased significantly with C. mukul treatment in group F+CM. The alterations observed in the activities of enzymes of carbohydrate and lipid metabolisms and contents of hepatic tissue lipids in group F rats were significantly restored to near normal values by C. mukul treatment in group F+CM. In conclusion, our study demonstrated that C. mukul treatment is effective in preventing fructose-induced insulin resistance and hypertriglyceridemia while attenuating the fructose induced alterations in carbohydrate and lipid metabolisms by the extract which was further supported by histopathological results from liver samples which showed regeneration of the hepatocytes. This study suggests that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it.

Hypoglycemic and hypolipidemic effect of Vaccinium myrtillus L. leaf and Phaseolus vulgaris L. seed coat extracts in diabetic rats.

The aim of this study was to examine the hypoglycemic and hypolipidemic effects of Vaccinium myrtillus L. leaf (VLE) and Phaseolus vulgaris L. seed coat (PCE) plant extracts, containing polyphenolic compounds, on carbohydrate and lipid metabolism in Wistar rats with streptozotocin (STZ) and high-fructose diet (HFD)-induced diabetes. Male Wistar rats with STZ and HFD-induced diabetes were fed with or without VLE or PCE for 50d. At different intervals, blood glucose and body weight were recorded. Blood samples were used to determine glycated hemoglobin (HbA) and parameters of lipid profile in serum. Additionally, the levels of serum diene conjugates and malondialdehyde were assessed. Results of HbA and blood glucose level analysis showed the ameliorative effect of VLE on carbohydrate metabolism in diabetic rats. Of the eight diabetic animals treated with bilberry leaf extract, four had normal HbA levels. A significant reduction was observed in VLE group in blood glucose level compared with control diabetic rats (level of hyperglycemia decreased to normal values in 50% of animals versus 0% in the control diabetic group). VLE treatment normalized parameters of lipid metabolism. There was no significant difference from the same parameters in the intact control group. Administration of PCE significantly (P<0.05) decreased the levels of plasma triacylglycerol (0.81±0.06mmol/L) and low-density lipoprotein (0.74±0.10mmol/L) in blood serum compared with the diabetic control group (1.36±0.13 and 1.85±0.30, respectively). Moreover, VLE and PLE showed an antioxidant effect on diene compounds in the blood serum of rats. A significant decrease was found in the plasma diene conjugate levels in PLE group (1.16±0.11nmol/mL) compared with control diabetic rats (2.09±0.21nmol/mL; P<0.05). There was no significant difference from the same parameter in the VLE and intact control groups. The set of results that was obtained in the present study reveals lipid-lowering and antioxidant action related to the administration of VLE and PCE in Wistar rats with diabetes, induced by STZ, in combination with a high-carbohydratediet. VLE to a certain extent also reduced hyperglycemia in diabetic animals.

Soybean β-conglycinin improves carbohydrate and lipid metabolism in Wistar rats

The effects of dietary soybean β-conglycinin on lipid metabolism and energy consumption were studied in Wistar adult rats. Rats were fed, a diet containing casein (control group) or β-conglycinin (β-conglycinin group), for 4 weeks. Carbohydrate consumption was higher and fat consumption was lower in the β-conglycinin group than in the control group, whereas the total energy consumption was the same between the two groups. Serum adiponectin was higher in the β-conglycinin group than in the control group. Serum triacylglycerol levels in the β-conglycinin group were significantly lower than those in the control group. The secretion rate of triacylglycerols from the liver after the administration of tyloxapol, an inhibitor of lipolysis, was significantly lower in the β-conglycinin group than in the control group. These results suggest the possibility that β-conglycinin exerts hypolipidemic effects through an acceleration in carbohydrate consumption associated with an increase in adiponectin in rats.

Vitamin B12 and omega-3 fatty acids together regulate lipid metabolism in Wistar rats

Our recent study indicates that maternal vitamin B12 and omega-3 fatty acid status influence plasma and erythrocyte fatty acid profile in dams. The present study examines the effects of prenatal and postnatal vitamin B12 and omega-3 fatty acid status on lipid metabolism in the offspring. Pregnant dams were divided into five groups: Control; Vitamin B12 deficient (BD); Vitamin B12 supplemented (BS); Vitamin B12 deficient group supplemented with omega-3 fatty acids (BDO); Vitamin B12 supplemented group with omega-3 fatty acids (BSO). The offspring were continued on the same diets till 3 month of age. Vitamin B12 deficiency increased cholesterol levels (p<0.01) but reduced docosahexaenoic acid (DHA) (p<0.05), liver mRNA levels of acetyl CoA carboxylase-1 (ACC-1) (p<0.05) and carnitine palmitoyltransferase-1 (CPT-1) (p<0.01) in the offspring. Omega-3 fatty acid supplementation to this group normalized cholesterol but not mRNA levels of ACC-1 and CPT-1. Vitamin B12 supplementation normalized the levels cholesterol to that of control but increased plasma triglyceride (p<0.01) and reduced liver mRNA levels of adiponectin, ACC-1, and CPT-1 (p<0.01 for all). Supplementation of both vitamin B12 and omega-3 fatty acid normalized triglyceride and mRNA levels of all the above genes. Prenatal and postnatal vitamin B12 and omega-3 fatty acids together play a crucial role in regulating the genes involved in lipid metabolism in adult offspring.

Short and long term in vivo effects of Cyclosporine A and Sirolimus on genes and proteins involved in lipid metabolism in Wistar rats

ObjectiveCyclosporine A (CsA) and sirolimus (SRL) are immunosuppressive agents (IA) associated with new onset diabetes after transplantation and dyslipidemia. We aim to evaluate the molecular effects of CsA (5mg/kg/day) and SRL (1mg/kg/day) treatment for 3 and 9weeks on lipid metabolism, in Wistar rats. Materials/MethodsLipolysis was evaluated in isolated adipocytes, while triglycerides (TG) and non-esterified fatty acid (NEFA) were measured in serum. Gene and protein expression involved in lipid metabolism was assessed in adipose tissue and liver. ResultsCsA and SRL treatments of rats for 3 and 9weeks increased isoproterenol-stimulated lipolysis by 5–9 fold and 4–6 fold in isolated adipocytes, respectively. While CsA increased adipocyte weight and diameter, as well as NEFA and TG levels in circulation after 9weeks, SRL treatment caused ectopic deposition of TG in the liver after 3weeks. Moreover, ACC1 and FAS protein expression was increased after 3weeks (>100%, p<0.01), while HSL was increased after 9weeks of CsA treatment. On the other hand, SRL decreased the expression of lipogenic genes, including ACC1 (50%, p<0.05), lipin1 (25%, p<0.05), PPAR-γ (42%, p<0.05) and SCD1 (80%, p<0.001) in adipose tissue, after 3weeks of treatment. ConclusionThe effects of both IAs on expression of lipolytic and lipogenic genes suggest that these agents influence lipid metabolism, thus contributing to the dyslipidemia observed during immunosuppressive therapy.

Molecular mechanisms underlying the effects of cyclosporin A and sirolimus on glucose and lipid metabolism in liver, skeletal muscle and adipose tissue in an in vivo rat model

Cyclosporin A (CsA) and sirolimus (SRL) are immunosuppressive agents (IAs) associated with dyslipidemia, insulin resistance and new onset diabetes after transplantation (NODAT). However, the molecular mechanisms involved are not fully understood. We investigated the effects of six-week treatment of either CsA or SRL on glucose and lipid metabolism in Wistar rats. The results show that, compared with vehicle-treated rats, SRL-treated rats were significantly lighter starting at week 5. CsA or SRL caused glucose intolerance, increased storage of lipids in the liver and skeletal muscle, and decreased the insulin-stimulated glucose uptake in isolated adipocytes. Furthermore, these agents significantly decreased genes involved in insulin action and glucose uptake, such as, IRS-1, Glut4 and Glut1, and increased genes and/or proteins involved in hepatic lipogenesis and gluconeogenesis, while decreasing them in adipose tissue. After either treatment PGC1α gene expression was down regulated in skeletal muscle, an important player in fatty acid oxidation. Moreover, there was an increase in IL-6 gene expression in adipose tissue in the SRL-treated rats, suggesting stimulation of lipolysis. The results of the present study suggest that CsA and SRL lead to metabolic alterations in liver, muscle and adipose tissue, which may contribute to the development of dyslipidemia and insulin resistance associated with immunosuppressive therapy.

Efficacy of silkworm (Bombyx mori L.) chrysalis oil as a lipid source in adult Wistar rats

The effects of silkworm chrysalis oil, rich in n-3 α-linolenic acid (ALA), on lipid metabolism in Wistar rats were investigated. The rats were fed diets containing 7% soybean oil (control), silkworm chrysalis oil (SWO), or fish oil (FO) for 8weeks. Plasma triglyceride and glucose levels were significantly lower in the SWO group after 8weeks compared to the control and FO groups. The total cholesterol and blood urea nitrogen levels were higher in the control group than in the SWO and FO groups at 8weeks post-consumption. However, aspartate amino transferase and alanine amino transferase levels were not significantly different among all groups. A higher arachidonic acid (AA) content was detected in the control group, while lower AA levels were observed with the increase in EPA and DHA in the SWO and FO groups. These results suggest that n-3 α-linolenic acid-rich silkworm chrysalis oil can improve hyperlipidaemia and hyperglycaemia.

Effects of Annurca Apple Fruit, a Southern Italy Cultivar, on Lipid Metabolism in Wistar Rats

Annurca apple fruit is commonly cultivated in southern Italy and undergoes a typical reddening treatment and, is notable for its high firmness and its characteristic flavour. Apples may have selective effects on abnormalities associated with the plurimetabolic syndrome. Therefore, the effects of 20% lyophilized Annurca apple supplementation on plasma and tissue lipids were investigated in Wistar rats. The experimental diets were equilibrated for sugar supply, containing 0.25g/100g cholesterol and provided only a third of the vitamin E requirement. The apple diet lowered plasma FFA and in parallel reduced triglyceride in heart and liver. Plasma leptin was also suppressed by the apple diet. In conclusion, despite their moderate fiber content, apples improve substantially the lipid status in Wistar rats, suggesting that other plant constituents such as the pectins are involved in these effects. Keywords: Wistar rats, apples, free fatty acids, leptin, lipoprotein, Annurca, Apple Fruit, Lipid Metabolism, plurimetabolic syndrome, tissue lipids, vitamin E, HDL species, triglyceride-lowering effect, insulinemia, glycemia, Leptin synthesis, physiological conditions, obesity, FFA-leptin interaction, ursane triterpen, Antioxidant activities, annurcoic acid, DPPH, MeLo, Heart lipids, Glycaemia

Gamma-oryzanol Ameliorates Insulin Resistance and Hyperlipidemia in Rats with Streptozotocin/nicotinamide-induced Type 2 Diabetes

Gamma-oryzanol is a component of rice bran oil (RBO) with purported health benefits. This study evaluated the effects of gamma-oryzanol on insulin resistance and lipid metabolism in Wistar rats with type 2 diabetes (T2DM). The rats were divided into three groups and consumed one of the following diets for 5 weeks: 15 % soybean oil (control group); 15 % palm oil (PO); and 15 % PO with the addition of 5.25 g gamma-oryzanol (POO). The results showed that PO markedly increased plasma low-density-lipoprotein cholesterol, plasma triglycerides, and hepatic triglyceride levels, but did not reduce the area under the curve for glucose and insulin significantly, compared with the control group. Adding gamma-oryzanol to PO improved the negative influence of PO on lipid metabolism in T2DM rats. In addition, gamma-oryzanol tended to increase insulin sensitivity in T2DM rats compared to control and PO groups. Longer-term studies are needed to evaluate these effects further.

Effect of Chlorella vulgaris on lipid metabolism in Wistar rats fed high fat diet.

This study was performed to investigate effects of Chlorella vulgaris on lipid metabolism in rats fed high fat diet. Sixty 6-week-old male Wistar rats were divided into two groups; normal diet group and high fat diet group, then the rats in each group were further divided into three subgroups and fed 0%, 5% and 10% (w/w) chlorella-containing diets, respectively, and raised for 9 weeks. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity and total protein and albumin concentration were not different among groups. Serum total lipids and liver TG concentration were significantly lower in 5% and 10% chlorella groups than 0% chlorella group in high fat diet groups (p<0.05). Serum TG, serum total cholesterol, liver total lipid and liver total cholesterol concentrations were significantly lower in 10% chlorella groups than 0% chlorella group in high fat diet groups (p<0.05). Fecal total lipid, TG and total cholesterol excretions were significantly higher in 5% and 10% chlorella groups than 0% chlorella groups in normal diet and high fat diet groups, respectively (p<0.05). These results suggest that Chlorella vulgaris is effective for prevention of dyslipidemia which may be due to the modulation of lipid metabolism and increased fecal excretion of lipid.

Fish Protein Hydrolysate Reduces Plasma Total Cholesterol, Increases the Proportion of HDL Cholesterol, and Lowers Acyl-CoA:Cholesterol Acyltransferase Activity in Liver of Zucker Rats

There is growing evidence that soy protein improves the blood lipid profiles of animals and humans. We compared the effects of fish protein hydrolysate (FPH), soy protein, and casein (control) on lipid metabolism in Wistar rats and genetically obese Zucker (fa/fa) rats. In Zucker rats, FPH treatment affected the fatty acid composition in liver, plasma, and triacylglycerol-rich lipoproteins. The mRNA levels of Delta 5 and Delta 6 desaturases were reduced by FPH and soy protein feeding compared with casein feeding. In Zucker rats both FPH and soy protein treatment reduced the plasma cholesterol level. Furthermore, the HDL cholesterol:total cholesterol ratio was greater in these rats and in the Wistar rats fed FPH and soy protein compared with those fed casein. Although fecal total bile acids were greater in soy protein-fed Zucker rats than in casein-fed controls, those fed FPH did not differ from the controls. However, the acyl-CoA:cholesterol acyltransferase activity was reduced in Zucker rats fed FPH and tended to be lower (P = 0.13) in those fed soy protein compared with those fed casein. Low ratios of methionine to glycine and lysine to arginine in the FPH and soy protein diets, compared with the casein diet, may be involved in lowering the plasma cholesterol concentration. Our results indicate that the effects of FPH and soy protein on fatty acid metabolism are similar in many respects, but the hypocholesterolemic effects of FPH and soy protein appear to be due to different mechanisms. FPH may have a role as a cardioprotective nutrient.

Impact of whole wheat flour and its milling fractions on the cecal fermentations and the plasma and liver lipids in rats.

The aim of the present work was to evaluate the cholesterol-lowering potency of the different milling fractions of whole wheat flour, by investigating the effects of these wheat fractions (white flour, whole flour, and bran) on digestive fermentations and lipid metabolism in Wistar rats. Compared to the control, which was fiber-free, the different cereal fractions did not affect the daily food intake or weight gain. The white flour and whole flour diets markedly enlarged the cecum and elicited acidic fermentations (pH approximately 6.2), whereas bran was less effective. It appears that white flour rather promoted propionate-rich fermentations (+62%), whereas bran favored butyrate-rich fermentations (+178%). White flour or bran did not significantly affect total steroid excretion, but whole flour was effective (+41%). Both white flour and whole flour decreased cholesterol in the d < 1.040 fraction, but only whole flour significantly lowered cholesterolemia. However, all the cereal diets significantly decreased liver lipids, whole flour being the most potent (-54%). In conclusion, the totality of the wheat grain is important for cholesterol- and triglyceride-lowering effects, and the splitting up of the grain alters its health effects.

The effects of dietary sugar-beet fibre and guar gum on lipid metabolism in Wistar rats.

This study investigates the mechanisms of action for the hypocholesterolaemic effects of sugar-beet fibre (SBF) and guar gum. Four groups of ten male Wistar rats were fed ad lib. on test diets containing either 100 g SBF or guar/kg, or control diets containing 100 g cellulose or wheat bran/kg for 28 d. Food intake, weight gain and food consumption ratios were unaffected by the diets. Circulating cholesterol and hepatic cholesterol concentrations were significantly lower in both SBF- and guar-fed groups compared with either cellulose- or bran-fed animals. Circulating triacylglycerol concentrations were significantly lower in SBF- and guar-fed animals, but total hepatic lipid concentrations and hepatic and adipose tissue lipogenesis rates were unaffected by the diets. Hepatic cholesterol-7 alpha-hydroxylase (EC 1.14.13.17) activities were significantly higher in the guar-fed animals compared with cellulose or bran control groups. Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.88) activities were unaffected. Circulating bile acid concentrations were significantly lower in SBF- and guar-fed animals and faecal bile acid output was significantly higher in the guar-fed group compared with bran- or cellulose-fed groups. This study supports the hypothesis that guar exerts its hypocholesterolaemic effect via intraluminal bile acid binding and loss of cholesterol from increased faecal bile acid excretion. The mechanism of action for the hypocholesterolaemic effect of SBF is less clear; the results of the present study point to a mechanism involving disruption of the enterohepatic bile acid circulation, possibly via changes in the rate of absorption of dietary lipid.