High-fat Diet-induced Oxidative Stress Research Articles

Hypoglycemic and Antioxidative Effects of Functional Rice Goami and Nokwon in High Fat-Fed Mice

Effects of newly developed functional rice grains Goami (high-amylose rice) and Nokwon (green-kerneled rice) on the glucose metabolism and antioxidative defense system in C57BL/6N mice under high fat diet condition were investigated. Animals were randomly divided into five groups (n = 8) and given experimental diets for eight weeks: normal control diet (NC), high fat diet (HF), and high fat diet supplemented with white rice (HF-WR), Goami rice (HF-GR), and Nokwon rice (HF-NR). At the end of the experimental period, the HF group exhibited markedly higher blood glucose level, insulin concentration, plasma lipid peroxidation and lower hepatic glycogen concentration than that exhibited by NC group. However, diet supplementation of Goami and Nokwon suppressed the high fat diet-induced hyperglycemia and oxidative stress through inhibition of the glucose-regulating enzymes and enhancement of the antioxidant enzymes activities. The results illustrate that the new functional rice Goami and Nokwon may be useful in the development of functional foods with preventive effect against high fat diet-induced hyperglycemia and oxidative stress.

Intake of jaboticaba peel attenuates oxidative stress in tissues and reduces circulating saturated lipids of rats with high-fat diet-induced obesity

The bioactive compounds of freeze-dried jaboticaba peel (FJP), serum lipids and the antioxidant status of rats fed high-fat diets containing different doses of FJP were evaluated. Obesity was induced and three groups of the obese animals received high-fat diet with 1%, 2% and 4% FJP added (J1, J2 and J4, respectively). The HPLC–DAD analyses of the polyphenols in the FJP showed four compounds: gallic acid, cyanidin 3-glucoside, ellagic acid, and quercetin. The serum saturated fatty acids were reduced in J1 and J4-fed animals. The antioxidant defenses of plasma were increased in the J2 and J4-fed animals. All the FJP diets prevented lipid peroxidation in the liver and increased its antioxidant defenses. Lipid peroxidation in brain decreased with an increasing FJP content in the diet. The antioxidant status of the kidneys of J2 and J4-fed animals increased. Thus, FJP could be an alternative to minimize the high-fat diet-induced oxidative stress and circulating saturated lipids.

Protective effects of azelaic acid against high-fat diet-induced oxidative stress in liver, kidney and heart of C57BL/6J mice

Excess fat intake induces hyperinsulinaemia, increases nutrient uptake and lipid accumulation, amplifies ROS generation, establishes oxidative stress and morphological changes leading to tissue injury in the liver, kidney and heart of high-fat diet (HFD)-fed mice. The effect of azelaic acid (AzA), a C9 α,ω-dicarboxylic acid, against HFD-induced oxidative stress was investigated by assaying the activities and levels of antioxidants and oxidative stress markers in the liver, kidney and heart of C57BL/6J mice. Mice were segregated into two groups, one fed standard diet (NC) and the other fed high-fat diet (HFD) for 15 weeks. HFD-fed mice were subjected to intragastric administration of AzA (80 mg/kg BW)/RSG (10 mg/kg BW) during 11-15 weeks. Glucose, insulin, triglycerides, hepatic and nephritic markers were analysed in the plasma and the activity of enzymatic, non-enzymatic antioxidants and lipid peroxidation markers were examined in the plasma/erythrocytes, liver, kidney and heart of normal and experimental mice. We inferred significant decrease in enzymatic and non-enzymatic antioxidants along with significant increase in glucose, insulin, hepatic and nephritic markers, triglycerides and lipid peroxidation markers in HFD-fed mice. Administration of AzA could positively restore the levels of plasma glucose, insulin, triglycerides, hepatic and nephritic markers to near normal. AzA increased the levels of enzymatic and nonenzymatic antioxidants with significant reduction in the levels of lipid peroxidation markers. Histopathological examination of liver, kidney and heart substantiated these results. Hence, we put forward that AzA could counteract the potential injurious effects of HFD-induced oxidative stress in C57BL/6J mice.

Platycodon grandiflorum root attenuates vascular endothelial cell injury by oxidized low-density lipoprotein and prevents high-fat diet–induced dyslipidemia in mice by up-regulating antioxidant proteins

We hypothesized that a Platycodon grandiflorum root (PG) ethyl acetate extract (PGEA) would help reduce the vascular cell injury caused by oxidized low-density lipoprotein (oxLDL) and prevent high-fat (HF) diet-induced dyslipidemia and oxidative stress by up-regulating antioxidant proteins. We investigated the protective effects of PGEA against vascular endothelial cell injury induced by oxLDL and dyslipidemia induced by an HF diet, and the mechanisms underlying these effects were studied. The protective effects of PGEA were investigated with respect to calf pulmonary arterial endothelial (CPAE) cell viability and the lactate dehydrogenase release during oxLDL treatment. The in vivo effects of PGEA were examined using C57BL/6 mice, which were fed an HF diet for 9 weeks. The HF diet was supplemented with 0, 25, or 75 mg/kg PGEA during the last 4 weeks of the experimental period. Histologic analyses of hepatic lipid accumulation were performed. The changes in antioxidant protein levels induced by PGEA, which protects against HF diet-induced oxidative stress, were measured using a proteomics approach. We found that PGEA exhibited antioxidant activity. In CPAE cells, PGEA inhibited both oxLDL-induced cell death and lactate dehydrogenase release. In the HF diet-induced obese mice that received PGEA, we observed significantly reduced plasma and hepatic lipid levels, demonstrating that PGEA has beneficial effects on hyperlipidemia. In addition, we found that PGEA caused the up-regulation of antioxidant proteins. These findings suggest that the antioxidant effects of PGEA may protect against oxidative stress-related diseases.

Antioxidant effect of grapevine leaves extract in rats fed a high fat diet

The purpose of this study was to investigate the effect of grapevine leaves extract(GLE) on oxidative stress in rats fed a high fat diet. The 4‐week‐old Sprague‐Dawley rats were divided into six groups; nomal diet group(N), nomal diet +1.0% GLE group(NG1.0), nomal diet +1.5% GLE group(NG1.5), high fat diet group(HF), high fat diet +1.0% GLE group(HFG1.0), high fat diet +1.5 GLE group(HFG1.5). Rats of each group were fed on the corresponding diets for 6 weeks. The thiobarbituric acid reactive substances(TBARS) in high fat and GLE‐treated groups revealed a significant reduction in liver, erythrocytes and plasma compared with the HF group. The erythrocytic activities of catalase(CAT), superoxide dismutase(SOD) and glutathione peroxidase(GSH‐Px) in HFG1.5 group were significantly higer than those of HF group. The hepatic activities of GSH‐Px and glutathione S‐transferase( GST) increased in GLE‐supplemented high fat group compered with HF group. The liver levels of retinol and tocopherol significantly increased in HFG1.5 group compared with those of HF group. Plasma tocopherol level in HFG1.5 group was significantly higher than HF group. These results indicate that grapevine leaves extract exerts a protective effect on high fat diet‐induced oxidative stress in rats. This research was supported by¡°Region‐specific agriculture Development project of RDA(Rural Development Administration), Republic of Korea.

Antihyperglycemic and antioxidative effects of Hydroxyethyl Methylcellulose (HEMC) and Hydroxypropyl Methylcellulose (HPMC) in mice fed with a high fat diet.

The effect of dietary feeding of hydroxyethyl methylcellulose (HEMC) and hydroxypropyl methylcellulose (HPMC) on the glucose metabolism and antioxidative status in mice under high fat diet conditions was investigated. The mice were randomly divided and given experimental diets for six weeks: normal control (NC group), high fat (HF group), and high fat supplemented with either HEMC (HF+HEMC group) or HPMC (HF+HPMC group). At the end of the experimental period, the HF group exhibited markedly higher blood glucose and insulin levels as well as a higher erythrocyte lipid peroxidation rate relative to the control group. However, diet supplementation of HEMC and HPMC was found to counteract the high fat-induced hyperglycemia and oxidative stress via regulation of antioxidant and hepatic glucose-regulating enzyme activities. These findings illustrate that HEMC and HPMC were similarly effective in improving the glucose metabolism and antioxidant defense system in high fat-fed mice and they may be beneficial as functional biomaterials in the development of therapeutic agents against high fat dietinduced hyperglycemia and oxidative stress.

Hypoglycemic and antioxidative effects of hydroxyethyl methylcellulose in mice fed with high fat diet

The effect of hydroxyethyl methylcellulose (HEMC) with different viscosities on the glucose metabolism and antioxidative defense system in high fat-fed mice was investigated. The mice were randomly divided into five dietary groups: normal control diet (NC), high fat diet (HF), and high fat diet supplemented with high viscosity (HF-HV), moderate viscosity (HF-MV), and low viscosity (HF-LV) HEMC fibers. After 6weeks, the HF group showed a marked increase in body weight gain, body fat, blood glucose concentration, insulin level, and erythrocyte lipid peroxidation rate relative to the NC group. However, supplementation of HEMC in the diet suppressed these high fat-induced hyperglycemia and oxidative stress through enhancement of the activities of hepatic glucokinase and antioxidant enzymes. The hypoglycemic and antioxidative effects increased with increased viscosity of the HEMC consumed. These results illustrate that HEMC with high viscosity may be useful in the management of high fat diet-induced hyperglycemia and oxidative stress.

High-fat diet-induced renal cell apoptosis and oxidative stress in spontaneously hypertensive rat are ameliorated by fenofibrate through the PPARα–FoxO3a–PGC-1α pathway

The peroxisome proliferator-activated receptor-α (PPARα) is a lipid-sensing transcriptional factor that has a role in gluco-oxidative stress and lipotoxicity. Forkhead box O (FoxO)s and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α are also known to regulate cell metabolism, cell cycle arrest, apoptosis and oxidative stress during stressful conditions. We evaluated whether PPARα-FoxOs-PGC-1α signaling in overfed spontaneously hypertensive rats (SHR) has a protective role in the kidney. Male SHR and Wistar-Kyoto rats (WKY) fed a high-fat diet (HFD) received treatment with fenofibrate, PPARα agonist or tempol, antioxidants for 12 weeks and were evaluated about the PPARα-FoxOs-PGC-1α pathway. The SHRs with an HFD had an elevated systolic pressure, plasma insulin, free fatty acid (FFA) and triglyceride (TGs) levels, and they had induced glucose intolerance as well as albuminuria, glomerular expansion and renal inflammation. An HFD caused the accumulation of intra-renal FFA and TGs and this was related to a decrease in the PPARα expression, the activation of phosphatidylinositol 3-kinase (PI3K)-Akt, phosphorylation of FoxO3a and decreases in the PGC-1α and estrogen-related receptor (ERR)-1α expressions, which suppressed the superoxide dismutase (SOD2) and Bcl-2 expressions and led to increases in oxidative stress and the number of apoptotic renal cells. Interestingly, administering fenofibrate or tempol to the HFD-induced SHRs reversed all of the renal phenotypes by increasing the PPARα expression with concomitant inactivation of the PI3K-Akt pathway, dephosphorylation of FoxO3a and activation of PGC-1α-ERR-1α signaling, and this all resulted in ameliorating the oxidative stress and apoptotic cell death. Our results demonstrated that PPARα agonists or antioxidants are associated with improvement of the circulating FFA and TGs levels and this prevents HFD-induced renal lipotoxicity and hypertension by the activation of PPARα and its downstream signals of both FoxO3a and PGC-1α.

Wheat bran xylooligosaccharides improve blood lipid metabolism and antioxidant status in rats fed a high-fat diet

Functional oligosaccharides have been used extensively both as food ingredients and pharmacological supplements. The objective of the present study was to evaluate effects of wheat bran xylooligosaccharides substituted with arabinose as novel functional oligosaccharides on blood lipid metabolism and antioxidant status in rats fed a high-fat diet for 6 weeks. The high-fat diet resulted in hyperlipidemia and an increase in oxidative stress, indicated by a significant rise in body weight, blood glucose and lipids levels, and malondialdehyde level of serum, liver and heart, and a significant decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) and antioxidant enzymes activity in them, however, supplementation of 5% wheat bran xylooligosaccharides had a beneficial effect on controlling body weight, improving blood glucose and lipid levels and increasing antioxidant status. These results demonstrated that wheat bran xylooligosaccharides might be effective in protecting humans against high-fat diet-induced oxidative stress.

Cholesterol-lowering action and antioxidative effects of microbial gum in C57BL/6N mice fed a high fat diet

The effect of feeding microbial gum on lipid metabolism and antioxidative status in high fat-fed C57BL/6N mice was investigated. The animals were randomly divided and fed with a normal control diet (NC group), a high fat diet (HF group), or a high fat diet supplemented with microbial gum (HFG group) for 7 weeks. At the end of the experimental period, the HF mice exhibited a marked increase in body weight, plasma and hepatic total cholesterol levels, and lipid peroxidation rate. Reduced activities of hepatic lipogenic and antioxidant enzymes were also observed in the HF group relative to that of the NC group. In contrast, feeding microbial gum counteracted the high fat diet-induced body weight gain, hypercholesterolemia, and oxidative stress by regulating antioxidant and lipogenic enzyme activities. These findings illustrate that microbial gum possess cholesterol-lowering action and antioxidant status-improving ability and may be useful for preventing and treating high fat diet-induced obesity and possibly reduce the risk of obesity-related diseases.

Lycopene Prevents Development of Steatohepatitis in Experimental Nonalcoholic Steatohepatitis Model Induced by High-Fat Diet

We investigated the preventive effect of lycopene on nonalcoholic steatohepatitis-induced by high-fat diet in rats. Forty male Sprague-Dawley rats were divided into 4 groups. They were fed standard diet, high-fat diet (HFD), high-fat diet plus lycopene at a dose of 2 mg/kg body weight and the high-fat diet lycopene at a dose of 4 mg/kg BW for a period of 6 weeks. Inflammation, steatosis, α-smooth muscle actin (α-SMA), and cytochrome P450 2E1 (CYP 2E1) expression increased significantly in the rats fed HFD and decreased in the rats administered by lycopene. Significantly elevated levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF α), and serum and liver malondialdehyde (MDA) were observed in rats fed the high-fat diet as compared to the control rats (P < .01). Supplementation with lycopene lowered serum MDA and tumor necrosis factor (TNF-α) levels and elevated liver GSH level (P < .001). Insulin resistance was higher in the rats fed HFD than in rats supplemented with lycopene. The data indicate that supplementation with lycopene can reduce high-fat diet-induced oxidative stress to the cells.

Improvement for High Fat Diet-Induced Hepatic Injuries and Oxidative Stress by Flavonoid-Enriched Extract from Nelumbo nucifera Leaf

Nelumbo nucifera Gaertn is widespread and a popular food in central and southern Taiwan. It has also been reported to possess different therapeutic effects, but the effects of N. nucifera leaf on lipid metabolism and liver function remain unclear. In this study, a high fat diet was used to induce hyperlipidemia, hypercholesterolemia, and fatty liver in hamster. The effects of flavonoid-enriched N. nucifera leaf extract supplement and two lipid-lowing drugs, silymarin and simvastatin, on the disorders induced by high fat diet were investigated. The results showed that a 10-week application of a high fat diet to hamsters led to significant increases of body weight, plasma lipid derivatives (triglyceride, total cholesterol, and lipoproteins), lipid peroxidation, and liver damage markers (plasma aspartate aminotransferase and alanine aminotransferase). Interestingly, flavonoid-enriched N. nucifera leaf extract supplement effectively ameliorated the high fat diet-induced lipid metabolic disorders as significantly as silymarin and simvastatin did. Moreover, the flavonoid-enriched supplement alleviated the high fat diet-induced accumulation of lipids in liver, the findings showing distinguishing mechanisms from the effects of silymarin and simvastatin. These results suggested that the flavonoid-enriched N. nucifera leaf extract supplement may significantly improve the high fat diet-induced abnormal blood lipids and liver damage as significantly as the common drugs. Consequently, it is suggested that the flavonoid-enriched N. nucifera leaf extract supplement is beneficial for the improvement of lipid metabolisms and the alleviation of liver damage in high fat diet treatment.

Effect of gallic acid on high fat diet-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats

Gallic acid (GA) is a naturally abundant plant phenolic compound in the human diet and is known to reduce the risk of disease. In this study, the anti-obesity effect of GA in an animal model of diet-induced obesity was investigated. Obesity was induced in male Wistar rats by feeding them a high-fat diet (HFD). GA was given as a supplement at the levels of 50 and 100 mg/kg rat for a period of 10 weeks. The results showed that the body weight, organ weight of the liver and adipose tissue weights of peritoneal and epididymal tissues in the HFD+GA groups were significantly decreased as compared with the HFD group. Serum TAG, phospholipid, total cholesterol, LDL-cholesterol, insulin and leptin levels in the HFD+GA groups were significantly decreased as compared with the HFD group. Histological study showed that the lipid droplets of rats with HFD+GA diets were significantly smaller than those with HFD diets. Hepatic TAG and cholesterol levels in HFD+GA groups were significantly decreased as compared with the HFD group. Moreover, the consumption of GA reduced oxidative stress and GSSG content and enhanced the levels of glutathione, GSH peroxidase, GSH reductase and GSH S-transferase in the hepatic tissue of rats with HFD-induced obesity. These results demonstrate that intake of GA can be beneficial for the suppression of HFD-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats.