Sulforaphane ameliorated oxidative stress, inflammatory release and obesity hormones abnormalities induced by high fructose and or high fat diet in rats

The present study aims to investigate the effectiveness of psyllium husk, green coffee, orange peel and their mixture on obesity Induced by high fat diet (HFD) in rats. Rats (n= 72 rats), were divided into two main groups, the first group, normal control, (Group 1, 6 rats) still fed on basal diet (BD) and the other main group (66 rats) was used for obesity induction by feed with HFD for four weeks then classified into eleven equal sub groups as follow:. Group 2 (G2), model control, fed on BD only as a positive control (rats with obesity), groups (3-10), fed on BD containing 2.5 and 5.0% of psyllium husk, green coffee, orange peel and their mixture, and groups (11-12) fed on BD containing 1 and 2% of CHROMAX (one of the dietary supplements commonly used in obesity management) for comparative study. Rats feeding on HFD (model control) for 4 weeks leads to increase the BWG, FI and FER than the normal group by the rate of 161.7, 47.6 and79.1%, respectively. Biochemical analysis data indicated that obesity induced a significant (p≤0.05) decrease the hemoglobin (-34.4%) and RBCs (-46.7%), serum albumin (-63.9%) and globulin (-51.7%), increased liver functions enzymes activities (AST, 147%, ALT 163.2% and ALP, 107.6%), blood glucose (151.5%), serum lipid profile (TGs, 83.3%, TC, 75.9% and LDL-c , 200.1%) compared to normal controls. Intervention with selected plant parts in feeding rats protocol for 4 weeks led to significantly (p≤0.05) improvement on the all biological and biochemical parameters of the obese rats by different rates. The best results for all previous measures were recorded in the groups of rats that were fed on a mixture of selected plant parts, followed by the groups that were fed on green coffee, orange peel and psyllium husks, respectively. Also, the feeding intervention with a mixture of plant parts was more effective in obesity treatment when compared to CHROMAX. In conclusion, the results of present study provide a basis for the use of selected plant parts for the prevention or early treatment of obesity and its related complications, but completing this important topic requires the necessity of conducting more studies and research in the future.

BackgroundThe composition of a diet can influence myocardial metabolism and development of left ventricular hypertrophy (LVH). The impact of a high-fat diet in chronic left ventricular volume overload (VO) causing eccentric LVH is unknown. This study examined the effects of chronic ingestion of a high-fat diet in rats with chronic VO caused by severe aortic valve regurgitation (AR) on LVH, function and on myocardial energetics and survival.MethodsMale Wistar rats were divided in four groups: Shams on control or high-fat (HF) diet (15 rats/group) and AR rats fed with the same diets (ARC (n = 56) and ARHF (n = 32)). HF diet was started one week before AR induction and the protocol was stopped 30 weeks later.ResultsAs expected, AR caused significant LV dilation and hypertrophy and this was exacerbated in the ARHF group. Moreover, survival in the ARHF group was significantly decreased compared the ARC group. Although the sham animals on HF also developed significant obesity compared to those on control diet, this was not associated with heart hypertrophy. The HF diet in AR rats partially countered the expected shift in myocardial energy substrate preference usually observed in heart hypertrophy (from fatty acids towards glucose). Systolic function was decreased in AR rats but HF diet had no impact on this parameter. The response to HF diet of different fatty acid oxidation markers as well as the increase in glucose transporter-4 translocation to the plasma membrane compared to ARC was blunted in AR animals compared to those on control diet.ConclusionsHF diet for 30 weeks decreased survival of AR rats and worsened eccentric hypertrophy without affecting systolic function. The expected adaptation of myocardial energetics to volume-overload left ventricle hypertrophy in AR animals seemed to be impaired by the high-fat diet suggesting less metabolic flexibility.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2261-14-123) contains supplementary material, which is available to authorized users.

Coping style predicts the (in)sensitivity for developing hyperinsulinemia on a high fat diet in rats

Several studies have suggested that oxidative stress might cause and aggravate the inflammatory state associated with obesity and could be the link between excessive weight gain and its related disorders such as insulin resistance and cardiovascular diseases. Thus, antioxidant treatment has been proposed as a therapy to prevent and manage obesity and associated complications. Therefore, the aim of the present study was to investigate the effects of supplementation of a standard or high fat diet with the antioxidant lipoic acid (LA) during 56 days, on body weight gain, adiposity, feed efficiency and intestinal sugar absorption, in male Wistar rats. LA supplementation induced a lower body weight gain and adipose tissue size in both control or high fat fed rats accompanied by a reduction in food intake. The group fed on a high fat diet and treated with LA (OLIP group) showed a lower body weight gain than its corresponding Pair-Fed (PF) group (P < 0.05), which received the same amount of food than LA-treated animals but with no LA. In fact, LA induced a reduction on feed efficiency and also significantly decreased intestinal alpha-methylglucoside (alpha-MG) absorption both in lean and obese rats. These results suggest that the beneficial effects of dietary supplementation with LA on body weight gain are mediated, at least in part, by the reduction observed in food intake and feed efficiency. Furthemore, the inhibitory action of LA on intestinal sugar transport could explain in part the lower feed efficiency observed in LA-treated animals and therefore, highlighting the beneficial effects of LA on obesity.

BackgroundObesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity.AimTo investigate the development of obesity in response to a high fat diet (HFD) and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF) (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice) on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats.MethodWhite male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr), 30 rats fed a high-fat diet (HFD) for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD), the 2nd group HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10th week (start time for treatments) for 4 weeks.Body weight, lipid profile & renal function (urea, uric acid creatinine) ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB) the oxidative stress marker reduced glutathione (GSH), and Malondialdehyde (MDA) catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed.ResultsData showed that feeding HFD diet significantly increased final body weight, triglycerides (TG), total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile.Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia, hyperinsulinemia, and high insulin resistance (IR) significantly increased in HFD in comparison with the control group. The treatment with L-carnitine or HMF improved the condition. HFD elevated hepatic MDA and lipid peroxidation associated with reduction in hepatic GSH and catalase activity; whereas administration of L-carnitine or herbal extract significantly ameliorated these hepatic alterations.ConclusionHFD induced obesity associated with a disturbed lipid profile, defective antioxidant stability, and high values of IR parameters; this may have implications for the progress of obesity related problems. Treatment with L-carnitine, or HMF extract improved obesity and its associated metabolic problems in different degrees. Also HMF has antioxidant, hypolipidaemic insulin sensitizing effects. Moreover HMF might be a safe combination on the organs whose functions were examined, as a way to surmount the obesity state; and it has a distinct anti-obesity effect.

MP76-07 IMPAIRMENT IN P2X2 PURINERGIC SIGNALING AND UP-REGULATING AAPOPTOSIS, AUTOPHAGY AND PYROPTOSIS CONTRIBUTE TO BLADDER DYSFUNCTION AFTER LONG-TERM HIGH-FAT DIET

Bioactive proanthocyanidins have been reported to have several beneficial effects on health in relation to metabolic syndrome, type 2 diabetes, and cardiovascular disease. We studied the effect of grape seed proanthocyanidin extract (GSPE) in rats fed a high fat diet (HFD). This is the first study of the effects of flavonoids on the liver proteome of rats suffering from metabolic syndrome. Three groups of rats were fed over a period of 13 weeks either a chow diet (control), an HFD, or a high fat diet supplemented for the last 10 days with GSPE (HFD + GSPE). The liver proteome was fractionated, using a Triton X-114-based two-phase separation, into soluble and membrane protein fractions so that total proteome coverage was considerably improved. The data from isobaric tag for relative and absolute quantitation (iTRAQ)-based nano-LC-MS/MS analysis revealed 90 proteins with a significant (p < 0.05) minimal expression difference of 20% due to metabolic syndrome (HFD versus control) and 75 proteins due to GSPE treatment (HFD + GSPE versus HFD). The same animals have previously been studied (Quesada, H., del Bas, J. M., Pajuelo, D., Díaz, S., Fernandez-Larrea, J., Pinent, M., Arola, L., Salvadó, M. J., and Bladé, C. (2009) Grape seed proanthocyanidins correct dyslipidemia associated with a high-fat diet in rats and repress genes controlling lipogenesis and VLDL assembling in liver. Int. J. Obes. 33, 1007-1012), and GSPE was shown to correct dyslipidemia observed in HFD-fed rats probably through the repression of hepatic lipogenesis. Our data corroborate those findings with an extensive list of proteins describing the induction of hepatic glycogenesis, glycolysis, and fatty acid and triglyceride synthesis in HFD, whereas the opposite pattern was observed to a large extent in GSPE-treated animals. GSPE was shown to have a wider effect than previously thought, and putative targets of GSPE involved in the reversal of the symptoms of metabolic syndrome were revealed. Some of these novel candidate proteins such as GFPT1, CD36, PLAA (phospholipase A(2)-activating protein), METTL7B, SLC30A1, several G signaling proteins, and the sulfide-metabolizing ETHE1 and SQRDL (sulfide-quinone reductase-like) might be considered as drug targets for the treatment of metabolic syndrome.

Background and AimsObesity promotes cardiac and cerebral microcirculatory dysfunction that could be improved by incretin-based therapies. However, the effects of this class of compounds on neuro-cardiovascular system damage induced by high fat diet remain unclear. The aim of this study was to investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by high fat diet in Wistar rats.Methods and ResultsWe have evaluated fasting glucose levels and insulin resistance, heart rate variability quantified on time and frequency domains, cerebral microcirculation by intravital microscopy, mean arterial blood pressure, ventricular function and mitochondrial swelling. High fat diet worsened biometric and metabolic parameters and promoted deleterious effects on autonomic, myocardial and haemodynamic parameters, decreased capillary diameters and increased functional capillary density in the brain. Biometric and metabolic parameters were better improved by glucagon like peptide-1 (GLP-1) compared with dipeptdyl peptidase-4 (DPP-4) inhibitor. On the other hand, both GLP-1 agonist and DPP-4 inhibitor reversed the deleterious effects of high fat diet on autonomic, myocardial, haemodynamic and cerebral microvascular parameters. GLP-1 agonist and DPP-4 inhibitor therapy also increased mitochondrial permeability transition pore resistance in brain and heart tissues of rats subjected to high fat diet.ConclusionIncretin-based therapies improve deleterious cardiovascular effects induced by high fat diet and may have important contributions on the interplay between neuro-cardiovascular dynamic controls through mitochondrial dysfunction associated to metabolic disorders.

Non-alcoholic fatty liver disease (NAFLD) has become a major challenge to the healthcare system. This study was designed to evaluate the effect of the triterpenoid-rich fraction (TF) from Ilex hainanensis Merr. on NAFLD. Male Sprague-Dawley (SD) rats were fed a normal diet (control) or high fat diet (NAFLD model). After four weeks, the high fat diet group was orally administrated TF (250 mg/kg) for another two weeks. High fat diet fed rats displayed hyperlipidemia and a decline in liver function compared with control. However, administration with TF could effectively improve these symptoms, as demonstrated by decreasing the plasma levels of triglyceride (p <0.05), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.05), alanine transaminase (p < 0.05), aspartate aminotransferase (p < 0.01), liver index (p < 0.05) and insulin resistance index (p < 0.05) while increasing the high-density lipoprotein cholesterol (p < 0.05). Meanwhile, histopathological examination of livers also showed that TF could reduce the incidence of liver lesions induced by high fat diet. Furthermore, TF could alleviate oxidative stress and inflammation status indicated by the decline malondialdehyde and superoxide dismutase levels (p < 0.01, both) and levels of interleukin 6 and tumor necrosis factor-α (p < 0.05). In addition, immunohistochemistry showed TF evidently elevated the peroxisome proliferator-activated receptor (PPARα) expression (p < 0.01), while it diminished the Cytochrome P450 2E1 (CYP2E1) expression (p < 0.01) in liver. These results demonstrate that TF has potential ability to protect liver against NAFLD by regulating lipids metabolism and alleviating insulin resistance, inflammation and oxidative stress. This effect might be associated with regulating PPARα and CYP2E1 expression.

Aim: The effect of aqueous extract of Costus afer stems on total protein, albumin,globulin, total and&#x0D; conjugated bilirubin levels in diet induced hyperlipidemic rats were studied.&#x0D; Methodology: Wistar albino male rats (100-135 g) were randomly distributed into 7 groups of 12 rats each. Group I was fed with standard diet as normal control rats and all the other groups were fed with high fat diet (10 g eggyolk/day) for 2 weeks. The plant extract was administered orally at different concentrations of 400, 800 and 1600mg/kg b.w alone and also in combination with the reference drug, Atorvastatin® (0.26mg) to the treatment groups for four weeks. The serum proteins and bilirubin were observed at specific intervals (2 weeks).&#x0D; Results: The results revealed significant (p&lt;0.05) increase in the total protein, albumin and globulin concentration after 2 weeks of feeding with high fat diet in rats which were in groups IV and V as compared to normal control rats. Treatment of rats with plant extract showed no significant difference in the total protein concentration of hyperlipidemic test rats while the albumin concentration of rats in group VII increased significantly when compared to the normal and hyperlipidemic control rats. There was no significant difference in the globulin concentration of hyperlipidemic treated rats. After 2nd and 4th week of treatment, the total bilirubin concentrations of rats in groups V and VI (HTR on aqueous extract, 1600 mg/kg and HTR on aqueous extract, 800 mg/kg) decreased significantly when compared with normal and hyperlipidemic control rats. After 2 weeks of treatment, the conjugate bilirubin concentration of rats in group VI (HTR on aqueous extract, 1600 mg/kg) significantly (p&lt;0.05) decreased when compared to the hyperlipidemic control rats.&#x0D; Conclusions: Hence, this shows that Costus afer stem extract does not have any deleterious effect on tissues and on the analyzed parameters.

Ingestion of cocoa ameliorates endothelial dysfunction in mesentery arterioles induced by high fat diet in rats: An in vivo intravital microscopy study

Objective. Currently, no agent has been conclusively demonstrated to prevent the progression of non-alcoholic steatohepatitis (NASH). Chitosan, a natural product derived from chitin, was thought to possess hypocholesterolemic properties. The aim of this study was to evaluate the potential effects of chitosan on nutritional steatohepatitis in rats. Material and methods. Rats were fed with a high fat diet for 4 weeks to develop NASH that was confirmed by liver biopsy, and then 4 weeks of chitosan was given. Serum chemistry and liver histology were assessed and the steatoinflammatory mechanisms were studied. Results. Chitosan significantly protected against high fat diet-induced hepatic steatohepatitis. This effect was associated with repressed serum levels of total protein (TP), globulin (GLO), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total cholesterol (TC) and low-density lipoprotein (LDL). Chitosan elevated the serum levels of high-density lipoprotein (HDL) and the ratio of albumin to globulin. Furthermore, increased TNF-α, lipoemia, hyperinsulinemia, hyperleptinemia and hypoadiponectin in NASH were significantly ameliorated by treatment with chitosan. Conclusions. Chitosan effectively attenuated the steatohepatitis induced by a high fat diet. The therapeutic effect of chitosan on NASH may be activated through exerting an influence on adipokines.

PurposeThis study aims to scrutinize the efficacy of chitosan (CT) on cardio-lipotoxic responses elicited by a high-fat diet (HF).Design/methodology/approachThirty-six male Wistar rats were distributed across six groups (n = 6): normal diet (ND), HF, ND-5%CT, HF-1%CT, HF-3%CT and HF-5%CT, for seven weeks. Blood and cardiac tissues were processed for biochemical, immunohistochemical and histopathological analyses.FindingsIngestion of HF induced hyperlipidaemia and lipid accumulation, leading to increased body and heart weight by 70.5% (p < 0.0001) and 124% (p = 0.0021), respectively, compared to ND-groups. Cardiac damage markers (creatine kinase, lactate dehydrogenase and malondialdehyde) were higher in the HF-group compared to control rats. Also, atherogenic and coronary risk indices were significantly elevated by 155% (p = 0.0044) and 174% (p = 0.0008), respectively, compared to control rats. Rats fed HF had significantly reduced cardiac antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and elevated expression of NF-κB-p65 and p53 (p < 0.0001) in the cardiac tissues. Histology revealed lipid inclusions in the cardiac tissues of HF-groups. CT (1%–5%) prevented hyperlipidaemia, lipid accumulation, oxidative stress and cardiac damage in HF-fed rats, while greatly improving the histology of the cardiac tissues in HF-fed rats in a dose-dependent manner.Originality/valueTo the best of the authors’ knowledge, this is the first report of the effects of CT against cardio-lipotoxicity elicited by HF diet ingestion. The findings suggest that CT may present a safe therapeutic alternative for managing complications arising from cardio-lipotoxicity.

Endoplasmic reticulum (ER) stress is involved in the development of glucose homeostasis impairment. When ER stress occurs, the unfolded protein response (UPR) is activated to cope with it. One of the UPR components is WFS1 (Wolfram syndrome 1), which plays important roles in ER homeostasis and pancreatic islets glucose-stimulated insulin secretion (GSIS). Accordingly and considering that feeding high-fat food has a major contribution in metabolic disorders, this study aimed to investigate the possible involvement of pancreatic ER stress in glucose metabolism impairment induced by feeding high-fat diet (HFD) in male rats. After weaning, the rats were divided into six groups, and fed on normal diet and HFD for 20 weeks, then 4-phenyl butyric acid (4-PBA, an ER stress inhibitor) was administered. Subsequently, in all groups, after performing glucose tolerance test, the animals were dissected and their pancreases were removed to extract ER, islets isolation and assessment of GSIS. Moreover, the pancreatic ER stress [binding of immunoglobulin protein (BIP) and enhancer-binding protein homologous protein (CHOP)] and oxidative stress [malondialdehyde (MDA), glutathione (GSH) and catalase] biomarkers as well as WFS1 expression level were evaluated. HFD decreased pancreatic WFS1 protein and GSH levels, and enhanced pancreatic catalase activity, MDA content, BIP and CHOP protein and mRNA levels as well as Wfs1 mRNA amount. Accordingly, it increased BIP, CHOP and WFS1 protein levels in the extracted ER of pancreas. In addition, the HFD caused glucose intolerance, and decreased the islets’ GSIS and insulin content. However, 4-PBA administration restored the alterations. It seems that, HFD consumption through inducing pancreatic ER stress, altered WFS1 expression levels, reduced the islets’ GSIS and insulin content and finally impaired glucose homeostasis.

The objective of this study was to investigate cellular apoptosis in prenatal glucocorticoid overexposure and a postnatal high fat diet in rats. Pregnant Sprague-Dawley rats at gestational days 14 to 21 were administered saline (vehicle) or dexamethasone and weaned onto either a normal fat diet or a high fat diet for 180 days; in total four experimental groups were designated, i.e., vehicle treated group (VEH), dexamethasone treated group (DEX), vehicle treated plus high-fat diet (VHF), and dexamethasone treated plus high-fat diet (DHF). Chronic effects of prenatal liver programming were assessed at postnatal day 180. The apoptotic pathways involved proteins were analyzed by Western blotting for their expressions. Apoptosis and liver steatosis were also examined by histology. We found that liver steatosis and apoptosis were increased in the DHF, DEX, and VHF treated groups, and that the DHF treated group was increased at higher levels than the DEX and VHF treated groups. The expression of leptin was decreased more in the DHF treated group than in the DEX and VHF treated groups. Decreased peroxisome proliferator-activated receptor-gamma coactivator 1α, phosphoinositide-3-kinase, manganese superoxide dismutase and increased malondialdehyde expression levels were seen in DHF treated group relative to the DEX treated group. The DHF treated group exhibited higher levels of oxidative stress, apoptosis and liver steatosis than the DEX treated group. These results indicate that the environment of high-fat diet plays an important role in the development of liver injury after prenatal stress.