Different Sources of Dietary Magnesium Supplementation Reduces Oxidative Stress by Regulation Nrf2 and NF-κB Signaling Pathways in High-Fat Diet Rats.

Hypophagia induced by inflammation is associated with Janus kinase (JAK)-2/signal transducer and activator of transcription (STAT) 3 signaling pathway, and leptin-mediated hypophagia is also mediated by JAK2-STAT3 pathway. We have previously reported that lipopolysaccharide (LPS) did not reduce food intake in leptin-resistant high-fat diet (HFD) rats but maintained body weight loss. We investigated whether changes in p-STAT3 expression in the hypothalamus and brain stem could account for the desensitization of hypophagia in HFD animals after a low LPS dose (100 μg/kg). Wistar rats fed standard diet (3.95 kcal/g) or HFD (6.3 kcal/g) for 8 wk were assigned into control diet-saline, control diet-LPS, HFD-saline, and HFD-LPS groups. LPS reduced feeding in the control diet but not HFD. This group showed no p-STAT3 expression in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH), but sustained, though lower than control, p-STAT3 in the nucleus of the solitary tract (NTS) and raphe pallidus (RPa). LPS decreased body weight in HFD rats and increased Fos expression in the NTS. LPS increased body temperature, oxygen consumption, and energy expenditure in both control diet and HFD rats, and this response was more pronounced in HFD-LPS group. Brown adipose tissue (BAT) thermogenesis and increased energy expenditure seem to contribute to body weight loss in HFD-LPS. This response might be related with increased brain stem activation. In conclusion, LPS activates STAT3-mediated pathway in the hypothalamus and brain stem, leading to hypophagia, however, LPS effects on food intake, but not body weight loss, are abolished by leptin resistance induced by HFD. The preserved STAT3 phosphorylation in the brain stem suggests that unresponsiveness to LPS on STAT3 activation under HFD might be selective to the hypothalamus.

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

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.

Background: The combination of Euphorbia milii (E. milii) flowers and Propolis (tala) of Apis cerana in tea form or EMP tea evidently acts as an immunomodulator, likewise a nontoxic agent for liver and renal in animal model and healthy people during Covid-19 pandemic. Moreover, total cholesterol and MMP-8 level in high fat diet (HFD) rats decreased in relation to the EMP tea. Thus, this study aimed to prove EMP tea in preventing atherosclerosis through molecular aspect in the mRNA of NF-kB and histology aspect in the number of foam cells at HFD rats. Material and Methods: a total of 28 male rats, 100-200 grams in weight (g BW), were sorted into four groups (K0, P1, P2, and P3). After adaptation for a week, K0 were given standard diet; P1 were given standard diet and EMP tea 40 mg/100 g BW daily, while P2 were given HFD 2 g/200 g BW daily; P3 were given HFD 2 g/200 g BW daily and EMP tea 40 mg/ 100 g BW daily for 30 days. Rats were sacrificed at day 31, aorta was collected then subjected to qRT-PCR to measure NF-kB and histological examination to evaluate foam cells. Data are shown in mean and standard deviation (SD). Results: The mRNA of NF- kB level at K0 (0.48 ± 0.28) fg/µl; P1(0.54 ± 0.05) fg/µl; P2 (0.66 ± 0.13) fg/µl; P3 (0.16 ± 0.07) fg/µl. There was a significant difference in the mRNA of NF- kB level (p<0.05) between K0 vs P3; P1 vs P2; P1 vs P3; and P2 vs P3. While the number of foam cells at K0 (0.43 ± 0.2) cells/fv; P1 (0.57 ± 0.2) cells/fv; P2 (54 ± 2.34) cells/fv and P3 (17 ± 2.05) cells/fv. There was a significant difference (p<0.05) in foam cells between K0 vs P2; K0 vs P3; P1 vs P2; P1 vs P3; and P2 vs P3. Conclusion: The mRNA of NF-kB and the number of foam cells in the rat aorta were lower in the administration of EMP tea with doses of 40 mg/100 g BW daily for 30 days in HFD rats.

Increased adiposity is strongly associated with inflammation. Prior studies have shown that feeding rats a high fat diet (HFD) leads to increased adiposity and inflammation, including elevated circulating tumor necrosis factor alpha (TNFα). The current study was designed to further examine whether markers of inflammation and immune system activation are altered in HFD rats. Rats were fed either a normal chow or HFD for 6 weeks. Comparative whole transcriptome sequencing of isolated aorta from HFD and chow fed rats indicates a significant (p<0.05) 2.8‐fold decrease in the expression of interferon regulatory factor 4 (IRF4), a factor required for lymphocyte activation, suggesting the immune system of these animals is downregulated. Results from western blot analyses show no difference in the expression of the anti‐inflammatory heat shock proteins 60 or 70 (HSP60/70) in erythrocytes or plasma from HFD rats compared to rats fed normal chow (p>0.05). Unlike TNFα, urinary levels of the inflammatory mediator prostaglandin E2 are not different between HFD and chow rats (p>0.05). These findings suggest that, despite elevations in TNFα, the immune system of HFD rats may be partly downregulated. Further studies testing the agglutination response of plasma samples collected from HFD and chow rats will help to assess how well circulating leukocytes respond to immune challenges in overweight animals.

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.

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.

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.

A study on the effects of extruded sorghum bran (ESB) or raw sorghum bran (RSB) on biomarkers of glucose dysregulation, dyslipidemia, inflammation, and antioxidant potential induced by a high-fat diet (HFD) in rats was carried out. Four groups of male Wistar rats (six per group) consumed a basal diet (BD), which were supplemented with either lard at 310 g/kg (HFD) or lard and ESB at 180 g/kg (HFD + ESB) or lard and RSB (HFD + RSB), for 8 weeks. The intake of HFD supplemented with ESB or RSB hindered the fat storage in adipocytes of abdominal tissue, dyslipidemia and the loss of glucose homeostasis. A positive correlation between inflammation biomarkers (Interleukin-1β and Interleukin-6) and glucose homeostasis was observed, while a negative correlation between antioxidant capacity (TEAC) and Interleukin-1β and Interleukin-6 was observed. As a conclusion, the ESB or RSB may be intended as part of healthy diets.

Background: Dual Amylin and Calcitonin Receptor Agonists (DACRAs) are treatment candidates for obesity and type 2 diabetes. Recently, a once-weekly DACRA (KBP-A) showed promise, potentially due to its different exposure profile compared to daily DACRA (KBP). Parathyroid hormone, a G-protein-coupled receptor (GPCR) class B agonist, is an example of the exposure profile being critical to the effect. Since KBP and KBP-A also activate GPCR class B, we compared the effects of injection to continuous infusion of short-acting KBP and long-acting KBP-A in obese and diabetic rats to shed light on the role of exposure profiles. Methods: To explore the metabolic benefits of dose optimization, the following dosing profiles were compared in High Fat Diet (HFD)-fed Sprague–Dawley rats and diabetic Zucker Diabetic Fatty (ZDF) rats: (1) KBP dosed once-daily by injection or by continuous infusion in HFD and ZDF rats; (2) KBP injected once-daily and KBP-A injected once every 3rd day (Q3D) in HFD rats; (3) KBP-A injected Q3D or by infusion in ZDF rats. Results: KBP and KBP-A, delivered by either injection or infusion, resulted in similar weight and food intake reductions in HFD rats. In ZDF rats, injection of KBP improved glucose control significantly compared to infusion, while delivery of KBP-A by injection and continuous infusion was comparable in terms of glucose control. Conclusion: different dosing profiles of KBP and KBP-A had no impact on metabolic benefits in HFD rats. In diabetic ZDF rats, KBP by injection instead of infusion was superior, while for KBP-A the effects were similar.

Diet-induced obesity (DIO) in laboratory rodents can serve as a model with which to study the pathophysiology of obesity, but obesogenic diets (high-sugar and/or high-fat) are often poorly characterised and simplistically aimed at inducing metabolic derangements for the purpose of testing the therapeutic capacity of natural products and other bioactive compounds. Consequently, our understanding of the divergent metabolic responses to different obesogenic diet formulations is limited. The aim of the present study was to characterise and compare differences in the metabolic responses induced by low-fat, medium-fat/high-sugar and high-fat diets in rats through multivariate statistical modelling. Young male Wistar rats were randomly assigned to CON (laboratory chow, low-fat), OB1 (high-sugar, medium-fat) or OB2 (high-fat) dietary groups (n = 24 each) for 17 weeks, after which metabolic responses were characterised. Projection-based multivariate analyses (principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA)) were used to explore the associations between measures of body composition and metabolism. Furthermore, we conducted a systematic literature survey to examine reporting trends in rat dietary intervention studies, and to determine how the metabolic responses observed in the present study compared to other recently published studies. The OB1 and OB2 dietary regimens resulted in distinct metabolic profiles, with OB1 characterised by perturbations in insulin homeostasis and adipose tissue secretory function, while OB2 was characterised by altered lipid and liver metabolism. This work therefore confirms, by means of direct comparison, that differences in dietary composition have a profound impact on metabolic and pathophysiological outcomes in rodent models of DIO. However, through our literature survey we demonstrate that dietary composition is not reported in the majority of rat dietary intervention studies, suggesting that the impact of dietary composition is often not considered during study design or data interpretation. This hampers the usefulness of such studies to provide enhanced mechanistic insights into DIO, and also limits the translatability of such studies within the context of human obesity.

We investigated the effects of E. edulis bioproducts (lyophilized pulp [LEE], defatted lyophilized pulp [LDEE], and oil [EO]) on nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in rats. All products were chemically analyzed. In vivo, 42 rats were equally randomized into seven groups receiving standard diet, HFD alone or combined with EO, LEE, or LDEE. After NAFLD induction, LEE, LDEE, or EO was added to the animals' diet for 4 weeks. LEE was rich in polyunsaturated fatty acids. From LEE degreasing, LDEE presented higher levels of anthocyanins and antioxidant capacity in vitro. Dietary intake of LEE and especially LDEE, but not EO, attenuated diet-induced NAFLD, reducing inflammatory infiltrate, steatosis, and lipid peroxidation in liver tissue. Although both E. edulis bioproducts were not hepatotoxic, only LDEE presented sufficient benefits to treat NAFLD in rats, possibly by its low lipid content and high amount of phenols and anthocyanins.

The present investigation was to examine the in vivo antioxidant activity and lipid peroxidation activities of different extracts of aerial parts of Chomelia asiatica (Linn). High fat diet rats demonstrated fundamentally decreased the levels of tissues enzymatic antioxidant and non-enzymatic antioxidant (Glutathione). The level of thiobarbuturic acid reactive substance (TBARS) is reduced in high-fat diet (HFD) rats when compared and control group. Administration of ethyl acetate extract of Chomelia asiatica in high fat diet rats were indicated altogether (p&lt;0.001) increased the levels of antioxidant enzymes, for example, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and level of non enzymatic antioxidant glutathione (GSH) when contrasted and HFD rats (Group II). The ethyl acetate extract of C. asiatica in high fat diet rats were discovered lowered the concentration of TBARS when contrasted and HFD rats. In comparison of all the three extracts treated group with standard group, the ethyl acetate extract of C. asiatica showed significant (p&lt;0.001) result than that of other groups. Taking into account the outcomes, we concluded that the ethyl acetate extract of C. asiatica is a significant source of antioxidant, which may be useful in keeping the advancement of different oxidative stresses. &nbsp; Key words: Chomelia asiatica, in vivo antioxidant, lipid peroxidation, rats.

BackgroundIt has been demonstrated that activated islet stellate cells (ISCs) play a critical role in islet fibrogenesis and significantly contribute to the progression of type 2 diabetes mellitus. However, the key molecules responsible for ISCs activation have not yet been determined. This study aimed to identify the potential key genes involved in diabetes-induced activation of ISCs.MethodStellate cells were isolated from three 10-week-old healthy male Wistar rats and three Goto-Kakizaki (GK) rats. Cells from each rat were primary cultured under the same condition. A Genome-wide transcriptional sequence of stellate cells was generated using the Hiseq3000 platform. The identified differentially expressed genes were validated using quantitative real-time PCR and western blotting in GK rats, high fat diet (HFD) rats, and their controls.ResultsA total of 204 differentially expressed genes (DEGs) between GK. ISCs and Wistar ISCs (W.ISCs) were identified, accounting for 0.58% of all the 35,362 genes detected. After the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, the mRNA levels of these genes were further confirmed by real-time PCR in cultured ISCs. We then selected Fos, Pdpn, Bad as the potential key genes for diabetes-induced activation of ISCs. Finally, we confirmed the protein expression levels of FOS, podoplanin, and Bad by western blotting and immunofluorescence in GK rats, HFD rats, and their controls. The results showed that the expression level of FOS was significantly decreased, while podoplanin and Bad were significantly increased in GK.ISCs and HFD rats compared with controls, which were consistent with the expression of α-smooth muscle actin.ConclusionsA total of 204 DEGs were found between the GK.ISCs and W.ISCs. After validating the expression of potential key genes from GK rats and HFD rats, Fos, Pdpn, and Bad might be potential key genes involved in diabetes-induced activation of ISCs.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100–300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.