The Influence of Copper Nanoparticles on Neurometabolism Marker Levels in the Brain and Intestine in a Rat Model.

The aim of this study is to assess the effect of different forms and dosages of copper on the levels of markers depicting the neurodegenerative changes in the brain and the jejunum. The experiment was performed using 40 male Wistar rats fed a typical rat diet with two dosages of Cu used as CuCO3 (6.5 and 13 mg/kg diet) and dietary addition of two CuNP dosages (standard 6.5 and enhanced 13 mg/kg diet), randomly divided into four groups. The levels of neurodegenerative markers were evaluated. Nanoparticles caused a reduction in the level of glycosylated acetylcholinesterase (GAChE), an increase the level of acetylcholinesterase (AChE) and lipoprotein receptor-related protein 1 (LRP1), a reduction in ß-amyloid (ßAP) in the brain and in the intestine of rats and a reduction in Tau protein in the brain of rats. The highest levels of AChE, the ATP-binding cassette transporters (ABC) and LRP1 and lower levels of toxic GAChE, ß-amyloid, Tau, hyper-phosphorylated Tau protein (p-Tau) and the complex of calmodulin and Ca2+ (CAMK2a) were recorded in the tissues of rats receiving a standard dose of Cu. The neuroprotective effect of Cu can be increased by replacing the carbonate form with nanoparticles and there is no need to increase the dose of copper.

Chromium Nanoparticles Together with a Switch Away from High-Fat/Low-Fiber Dietary Habits Enhances the Pro-Healthy Regulation of Liver Lipid Metabolism and Inflammation in Obese Rats.

The study on Wistar rats was conducted to investigate the effects of a pharmacologically relevant dose 0.3 mg/kg body weight of chromium supplementation (commonly used picolinate or novel form as nanoparticles) and switching away from obesogenic dietary habits on the parameters of lipid metabolism, inflammation, and oxidative stress in liver and plasma. Favorable effects related to dietary changes from the obesogenic diet were considerably enhanced when the diet was supplemented with chromium nanoparticles. This combination exerted the strongest fat content and cholesterol reduction in the liver. Moreover, in this group, a favorable antioxidative effect was observed through GSH/GSSG elevation in the liver as well as ALT activity reduction in the plasma and IL-6 levels in the liver. The molecular mechanisms associated with regulating lipid metabolism, oxidative stress and inflammation might be related to lower expression of HIF-1α, COX-2, and LOX-1 and upregulation of PPARα in the liver. Supplementation with chromium nanoparticles without changes in the obesogenic diet also favorably affected lipid metabolism and oxidative stress in the liver; however, the examined effects were moderate. In conclusion, the favorable effects of switching from an obesogenic to a balanced diet on hepatic lipid metabolism, oxidative stress, and inflammation induced by an obesogenic diet might be enhanced by supplementation with chromium nanoparticles.

Immunonutritional Protease Inhibitors from T. durum and A. sativa Display Metabolic Similarities When Assayed on Human Macrophage-like Cells.

This study evaluated the immunonutritional effects caused by protease inhibitors from Avena sativa and Triticum durum to human macrophage-like cells. Macrophages were exposed (3 h) to extracts obtained from flours, and mitochondrial-associated oxygen consumption rates and inflammatory, metabolic, and proteome adaptations were quantified. Mass spectrometry 'm/z' signals of the extracts obtained from T. durum and A. sativa revealed molecular weights of 18-35 kDa and 16-22 kDa, respectively, for the compounds present at highest concentrations. Extracts from T. durum exhibited lower susceptibility to degradation by gastrointestinal enzymes than those from A. sativa: 9.5% vs 20.2%. Despite their different botanical origin, both extracts increased TLR4 expression. Metabolic protein levels were indicative of a decreased glycolytic to lactate flux in cell cultures upon stimulation with A. sativa extracts, which improved mitochondrial respiration in relation to those from T. durum. Principal components analysis confirmed relative similarities between immune-metabolic events triggered by immunonutritional ingredients in T. durum and A. sativa. Collectively, immunonutritional effects help to interpret the differences between both crops, worsening or improving, macrophage immune reactivity (tolerogenicity), and better control of inflammatory processes.

Dietary Hemp Seeds More Effectively Attenuate Disorders in Genetically Obese Rats than Their Lipid Fraction.

BACKGROUND: Hemp seeds are rich in PUFAs and other bioactives that can attenuate the development of obesity-related disorders; however, the extent to which their lipid fraction is responsible for this effect is unknown. OBJECTIVE: We hypothesized that hemp seed or hemp oil supplementation can attenuate genetically determined disorders and that the former are more effective in doing so. METHODS: Lean and obese male Zucker rats, aged 8 wk, weighing 174 ± 4.2 g and 223 ± 3.8 g, respectively, were allocated to 4 groups. The lean (LC) and obese controls (OC) were fed a standard diet, whereas the other 2 obese groups were fed a modified diet in which hemp oil (4% diet; O + HO) or hemp seeds (12% diet; O + HS) were included. All diets had the same proportions of protein (18%), fat (8%), and fiber (5%) and a similar carbohydrate proportion (∼52%). Diets fed to O + HO and O + HS had similar fatty acid profiles. After 4 wk, markers of gut and liver function, antioxidant status, and lipid metabolism were measured. RESULTS: The total SCFA concentration in the cecal digesta was lower in OC (64.8 ± 4.21 µmol/g) compared with LC (78.1 ± 2.83 µmol/g) (P ≤ 0.05), whereas it was greater in O + HS (89 ± 4.41 µmol/g) compared with LC, OC, and O + HO (69.7 ± 2.68 µmol/g) (P ≤ 0.05). Plasma total cholesterol was greater in OC (6.20 ± 0.198 mmol/L) and O + HO (5.60 ± 0.084 mmol/L) compared with LC (2.71 ± 0.094 mmol/L) (P ≤ 0.05); in O + HS, the concentration did not differ from the other groups (5.16 ± 0.278 mmol/L). The liver cholesterol concentration was greater in OC (1.79 ± 0.379 mg/g) compared with the other groups (1.28-1.43 mg/g) (P ≤ 0.05). Hepatic expression of peroxisome proliferator-activated receptor γ was lower in OC (11.9 ± 0.93 units) compared with LC (17.3 ± 1.3 units) (P ≤ 0.05), whereas it was greater in O + HS (19.2 ± 1.04 units) compared with OC and O + HO (14.0 ± 1.33 units) (P ≤ 0.05). CONCLUSIONS: Dietary hemp seeds more effectively attenuate metabolic disorders in genetically obese rats than the oil extracted from them, which suggests that the lipid fraction is only partly responsible for these effects.

Cannabis-derived cannabidiol and nanoselenium improve gut barrier function and affect bacterial enzyme activity in chickens subjected to C. perfringens challenge.

Revealing the multifocal mechanisms affecting cross-talk between Clostridium perfringens pathogenesis and the host response is an urgent need in the poultry industry. Herein, the activity of Cannabis sativa-derived cannabidiol (CBD) and selenium nanoparticles (Nano-Se) in modulating the host response to Clostridium perfringens challenge was investigated in broiler chickens subjected to a mild infection model. The infected chickens exhibited no clinical manifestations, confirming the potential hazard of pathogen transmission to the food chain in the commercial sector. However, both CBD and Nano-Se affected the responses of chickens to C. perfringens challenge. The beneficial actions of both agents were manifested in the upregulated expression of genes determining gut barrier function. Both CBD and Nano-Se promoted shifts in gut bacterial enzyme activity to increased energy uptake in challenged chickens and upregulated potential collagenase activity. There was no opposite effect of CBD and Nano-Se in mediating the host response to challenge, whereas an additive effect was evidenced on the upregulation of gene determining gut integrity. Collectively, these findings indicate that understanding the action mechanisms of CBD and Nano-Se is of great interest for developing a preventive strategy for C. perfringens infection in broilers.

Comparative Effects of Dietary Hemp and Poppy Seed Oil on Lipid Metabolism and the Antioxidant Status in Lean and Obese Zucker Rats.

The objective of this study was to compare the effects of the dietary inclusion of hemp seed oil (HO) and poppy seed oil (PO) on the lipid metabolism and antioxidant status of lean and genetically obese Zucker rats. The rats were fed a control diet for laboratory rodents or a modification with HO or PO. Both oils reduced body and epididymal fat and liver cholesterol levels and promoted oxidative stress in the liver of obese rats. The HO reduced plasma triglycerides and had a stronger liver cholesterol-lowering effect in obese rats than PO. In the lean rats, HO and PO had no effects on the body fat content, plasma lipid profile, or lipid metabolism in the liver. HO considerably elevated the content of α-linolenic acid in the liver and increased the liver ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) in the lean rats. In conclusion, the regular consumption of both oils increases the accumulation of essential fatty acids in the liver of healthy animals, whilst not having any adverse effects on the body, whereas in genetically obese rats, the effects of both dietary oils on the lipid metabolism and antioxidant status are unequivocal and only partially beneficial.

Protective Effects of a Strawberry Ellagitannin-Rich Extract against Pro-Oxidative and Pro-Inflammatory Dysfunctions Induced by a High-Fat Diet in a Rat Model.

Due to the demonstrated intestinal microbial transformation of strawberry ellagitannins (ET) into bioactive metabolites, in the current study on rats, we hypothesised that the dietary addition of a strawberry ET-rich extract (S-ET) to a high-fat diet (HFD) would attenuate disturbances in the redox and lipid status as well as in the inflammatory response. We randomly distributed 48 Wistar rats into six groups and used two-way analysis of variance (ANOVA) to assess the effects of two main factors-diet type (standard and high-fat) and ET dosage (without, low, and 3× higher)-applied to rats for 4 weeks. In relation to the hypothesis, irrespective of the dosage, the dietary application of ET resulted in the desired attenuating effects in rats fed a HFD as manifested by decreased body weight gain, relative mass of the epididymal pad, hepatic fat, oxidized glutathione (GSSG), triglycerides (TG), total cholesterol (TC), and thiobarbituric acid-reactive substances (TBARS) concentrations as well as desired modifications in the blood plasma parameters. These beneficial changes were enhanced by the high dietary addition of ET, which was associated with considerably higher concentrations of ET metabolites in the urine and plasma of rats. The results indicated that S-ET could be effectively used for the prevention and treatment of metabolic disturbances associated with obesity, dyslipidaemia, redox status imbalance, and inflammation.

The toxic effects of monosodium glutamate (MSG) - The involvement of nitric oxide, prostanoids and potassium channels in the reactivity of thoracic arteries in MSG-obese rats.

We investigated the potential effects of monosodium glutamate (MSG)-induced obesity with regards to nitric oxide and prostanoid production, as well as potassium channel function, in rat thoracic arteries. Newborn male Wistar rats were injected intraperitoneally with typically reported MSG (4.0 mg/g) once daily for 4 consecutive days. At 90 days postnatal, the rats were sacrificed and the thoracic aortas were evaluated for vascular responses and for prostanoid production. Nitric oxide was studied with calcium ionophore (A23187), acetylcholine (ACh) and sodium nitroprusside (SNP). The release of prostanoids was measured under basal and ACh-stimulated conditions, and the vasomotor effect of exogenous thromboxane A2 mimetic, U46619 was assessed. Potassium channel activities were analyzed using an NS1619 opener for BKCa channels and pinacidil for KATP channels. Arteries from MSG-obese rats exhibited a reduced maximal contraction to potassium chloride and hyper-responsiveness to U46619, suggesting that MSG also alters the responsiveness of vascular smooth muscles. The endothelium-dependent relaxation to ACh and A23817 was attenuated, suggesting low nitric oxide bioavailability. The hypersensitivity of arteries to an exogenous nitric oxide donor, SNP, occurred. The secondary contraction to A23817 was augmented, suggesting increased activation of the prostanoid receptor. The prostanoid release was increased in both basal- and acetylcholine-stimulated rings. In addition, down-regulation of KATP and BKCa channels influenced hyperpolarizing mechanisms. Our findings suggest that increased prostanoid production and hypersensitivity to thromboxane A2 together with down-regulation of potassium channels and low nitric oxide bioavailability may contribute to the increase in blood pressure found in adult MSG-obese male rats.

Raspberry Polyphenolic Extract Regulates Obesogenic Signals in Hepatocytes.

The aim of this in vitro study was to examine the effect of raspberry polyphenolic extract on the immune-metabolic molecular mechanisms activated by obesity-related signals in hepatocytes (HB-8965®). Alterations in endosomal/lysosomal activity (neutral red uptake assay, NR), the expression of selected genes involved with lipid oxidation, and metabolism and inflammation processes in the liver were studied. Hepatocytes were treated with plasma collected from Wistar rats that were fed a high-fat diet (HF), raspberry polyphenolic extract (PP), serine-type protease inhibitors as an agonist of TLR4 (TD) or a combination of PP with HF or TD treatments. The PP added to the experimental treatments modulated hepatic immune-metabolic mechanisms through the upregulation of STAT1, ANGPTL4, and CD44, as well as considerably reducing the NR uptake and downregulation of COX-2 and the multifunctional protein AhR. The kinetic analysis of AhR expression revealed that HF-related molecular mechanisms activated AhR mRNA expression earlier than PP initiated the regulatory effect. In conclusion, PP might be considered a valuable dietary agent that regulates obesity-related signals in hepatocytes. Moreover, taking AhR kinetic behavior into consideration, it can be assumed that PP might modulate the severity of the HF-induced downstream metabolic signaling of AhR.

Metabolism of strawberry mono- and dimeric ellagitannins in rats fed a diet containing fructo-oligosaccharides.

PURPOSE: We investigated the effects of dietary supplementation with strawberry extracts rich in ETs and fructo-oligosaccharides (FOS) on the intestinal microbiota and the formation of bacterial metabolites in the distal intestine, as well as the absorption of ET metabolites and antioxidant status in rats. METHODS: Rats were allocated into six groups of eight animals each and fed for 4 weeks with a control diet (group C), a control diet supplemented with FOS (group C + FOS) or modifications of these diets, in which a monomeric or dimeric ET-rich extract was added (groups ME and ME + FOS or DE and DE + FOS, respectively). RESULTS: The extract addition, the FOS addition and their interaction significantly affected the total and selected bacterial counts in the caecal digesta (all P < 0.005). The total bacterial count was the highest in group C + FOS, lower in group DE and the lowest in group ME + FOS (10.6, 10.3 and 8.52 log cells/g, respectively; P ≤ 0.05). The total caecal content of ET metabolites was higher in the ME and ME + FOS group than in the DE and DE + FOS group, respectively (67.8 and 89.5 vs. 13.0 and 18.0 µg/g, respectively; P < 0.001). The total plasma concentration of ET metabolites was higher in the ME + FOS and DE + FOS group than in the ME group (248 and 281 vs. 8.13 ng/mL, respectively; P < 0.001). CONCLUSIONS: ETs of the monomeric ET-rich extract are more prone to intestinal breakdown than those of the dimeric ET-rich extract, and absorption of their metabolites can be increased by dietary FOS; however, together, they evoke strong antibacterial activity.

Drought Induces Distinct Growth Response, Protection, and Recovery Mechanisms in the Maize Leaf Growth Zone.

Drought is the most important crop yield-limiting factor, and detailed knowledge of its impact on plant growth regulation is crucial. The maize (Zea mays) leaf growth zone offers unique possibilities for studying the spatiotemporal regulation of developmental processes by transcriptional analyses and methods that require more material, such as metabolite and enzyme activity measurements. By means of a kinematic analysis, we show that drought inhibits maize leaf growth by inhibiting cell division in the meristem and cell expansion in the elongation zone. Through a microarray study, we observed the down-regulation of 32 of the 54 cell cycle genes, providing a basis for the inhibited cell division. We also found evidence for an up-regulation of the photosynthetic machinery and the antioxidant and redox systems. This was confirmed by increased chlorophyll content in mature cells and increased activity of antioxidant enzymes and metabolite levels across the growth zone, respectively. We demonstrate the functional significance of the identified transcriptional reprogramming by showing that increasing the antioxidant capacity in the proliferation zone, by overexpression of the Arabidopsis (Arabidopsis thaliana) iron-superoxide dismutase gene, increases leaf growth rate by stimulating cell division. We also show that the increased photosynthetic capacity leads to enhanced photosynthesis upon rewatering, facilitating the often-observed growth compensation.

Dietary Supplementation with Raspberry Seed Oil Modulates Liver Functions, Inflammatory State, and Lipid Metabolism in Rats.

BACKGROUND: Although raspberry seed oil (RO) is rich in essential fatty acids, there is a lack of experiments assessing benefits of its consumption. OBJECTIVE: We investigated the effects of dietary supplementation with RO on healthy rats and rats with low-grade systemic inflammation, liver disorders, and dyslipidemia induced by a high-fat/low-fiber (HF/LF) diet. METHODS: Thirty-two rats were allocated into 4 groups of 8 rats each and fed for 8 wk a control (C; 7% lard and 5% cellulose) or HF/LF (21% lard and 2% cellulose) diet or modifications of these diets in which 7% RO replaced all (C+RO group) or a proportion of (HF/LF+RO group) the lard. Effects of diet and RO and their interaction on bacterial activity and metabolite formations in the distal intestine, liver fat and glutathione concentration, plasma lipid profile, transaminase activities, and plasma concentrations of C-reactive protein (CRP) and tumor necrosis factor α (TNF-α) were tested. RESULTS: Dietary RO decreased plasma alanine and aspartate transaminase activities (43.4 and 157 vs. 25.6 and 115 U/L, respectively; P < 0.05 and P < 0.005) and plasma TNF-α and triglyceride concentrations (132 pg/mL and 2.07 mmol/L vs. 86.5 pg/mL and 0.99 mmol/L, respectively; P < 0.05). In livers of the C+RO group, the fat concentration was decreased, whereas the glutathione to glutathione disulfide ratio was increased compared with the C group (30.1% and 6.20 µmol/g vs. 23.3% and 7.25 µmol/g, respectively; P ≤ 0.05); however, those differences were not observed between the HF/LF groups (P-interaction < 0.05). In the HF/LF+RO group, the plasma CRP concentration was lower than in the HF/LF group (88.1 vs. 765 pg/mL; P ≤ 0.05) and similar to that in the C and C+RO groups (158 and 128 pg/mL, respectively). CONCLUSION: Dietary RO improves plasma lipid profile and liver functions and reduces low-grade systemic inflammation in rats; however, the extent of these beneficial effects is partly dependent on the diet type.

Disparate metabolic effects of blackcurrant seed oil in rats fed a basal and obesogenic diet.

PURPOSE: It was hypothesised that blackcurrant seed oil beneficially modulates metabolic disorders related to obesity and its complications. The study also aimed to investigate the potentially adverse effects of an unbalanced diet on the distal intestine. METHODS: Male Wistar rats were randomly assigned to four groups of eight animals each and were fed a basal or obesogenic (high in fat and low in fibre) diet that contained either rapeseed oil (Canola) or blackcurrant seed oil. A two-way analysis of variance was then applied to assess the effects of diet and oil and the interaction between them. RESULTS: After 8 weeks, the obesogenic dietary regimen increased the body weight, altered the plasma lipid profile and increased the liver fat content and the plasma transaminase activities. In addition, the obesogenic diet decreased bacterial glycolytic activity and short-chain fatty acid formation in the distal intestine. Dietary blackcurrant seed oil improved the lipid metabolism by lowering liver fat accumulation and the plasma triglyceride concentration and atherogenicity as well by increasing the plasma HDL-cholesterol concentration. However, in rats fed an obesogenic diet containing blackcurrant seed oil, the plasma HDL-cholesterol concentration was comparable with both rapeseed oil-containing diets, and a significant elevation of the plasma transaminase activities was noted instead. CONCLUSIONS: The obesogenic dietary regimen causes a number of metabolic disorders, including alterations in the hindgut microbial metabolism. Dietary blackcurrant seed oil ameliorates the lipid metabolism; however, the beneficial effect is restricted when it is provided together with the obesogenic diet, and a risk of liver injury may occur.

Ellagitannins and Flavan-3-ols from Raspberry Pomace Modulate Caecal Fermentation Processes and Plasma Lipid Parameters in Rats.

Raspberry pomace is a source of polyphenols, which nutritional and health promoting properties are not sufficiently known. The aim of this 8-weeks study was to scrutinize if raspberry extracts (REs) with different ellagitannins to flavan-3-ols ratios might favorably affect the caecal fermentation processes and blood lipid profile in rats. Forty male Wistar rats were fed with a standard diet or its modification with two types of REs (E1 and E2) characterized by different ratios of ellagitannins to flavan-3-ols (7.7 and 3.1 for E1 and E2, respectively) and added to a diet at two dosages of polyphenolic compounds (0.15 and 0.30% of a diet; L and H treatments, respectively). Irrespective of polyphenols dietary level, both REs reduced the activity of bacterial ß-glucuronidase, increased production of butyric acid in the caecum and reduced triacylglycerols in blood plasma. The E1 treatment at both dosages caused more effective reduction in the concentration of ammonia and elevated acetate level in the caecal digesta than E2. On the other hand, only the E2 treatment lowered value of the atherogenic index when compared with control group. When comparing dosages of REs, a higher one was more potent to reduce the activity of bacterial ß-glucosidase, ß-, α-galactosidase and lowered value of the HDL profile in plasma. To conclude, REs may favorably modulate the activity of the caecal microbiota and blood lipid profile in rats; however, the intensity of these effects may be related to the dosages of dietary polyphenols and to their profile, e.g., ellagitannins to flavan-3-ols ratio.

Chromium nanoparticles improve bone turnover regulation in rats fed a high-fat, low-fibre diet.

The aim of the study was to investigate the effect of returning to a balanced diet combined with chromium picolinate (CrPic) or chromium nanoparticles (CrNPs) supplementation at a pharmacologically relevant dose of 0.3 mg/kg body weight on the expression level of selected genes and bone turnover markers in the blood and bones of rats fed an obese diet. The results of the study showed that chronic intake of a high-fat obesogenic diet negatively affects bone turnover by impairing processes of both synthesis and degradation of bones. The switch to a healthy diet proved insufficient to regulate bone metabolism disorders induced by an obesogenic diet, even when it was supplemented with chromium, irrespective of its form. Supplementation with CrPic with no change in diet stimulated bone metabolism only at the molecular level, towards increased osteoclastogenesis (bone resorption). In contrast, CrNPs added to the high-fat diet effectively regulated bone turnover by increasing both osteoblastogenesis and osteoclastogenesis, with these changes directed more towards bone formation. The results of the study suggest that unfavourable changes in bone metabolism induced by chronic intake of a high-fat diet can be mitigated by supplementation with CrNPs, whereas a change in eating habits fails to achieve a similar effect.

Gastrointestinal response to the early administration of antimicrobial agents in growing turkeys infected with Escherichia coli.

This study investigated the effects of the early administration of enrofloxacin (E) or doxycycline (D) for the first 5 consecutive days of life, or the continuous administration of the coccidiostat monensin (M) throughout the rearing period on gastrointestinal function in turkeys infected with avian pathogenic Escherichia coli (APEC) in an early or later stage of rearing. Experiment 1 lasted 21 d, and turkeys in groups E, D, and M were infected with APEC on d 15. Experiment 2 lasted 56 d, and it had a factorial arrangement of treatments where birds in groups E, D, and M were infected with APEC on d 15 or d 50. In both experiments, control groups (C) consisted of infected and uninfected birds without antibiotic or coccidiostat administration. On d 21 (Experiment 1) and d 56 (Experiment 2), 8 birds from each subgroup were killed, and the ileal and cecal digesta were sampled to analyze the activity of bacterial enzymes and the concentrations of short-chain fatty acids (SCFA). The experimental treatments did not affect the final body weight or body weight gain of birds. Both experiments demonstrated that APEC contributed to an increase in ammonia levels of the cecal digesta (means from 2 experiments: 0.311 vs. 0.225 mg/g in uninfected birds) and ileal pH (6.79 vs. 6.00) and viscosity (2.43 vs. 1.83 mPa⋅s). Moreover, the E. coli challenge enhanced the extracellular activity of several cecal bacterial enzymes, especially in older turkeys infected with APEC in a later stage of life. The continuous administration of monensin throughout the rearing period resulted in a weaker gastrointestinal response in older birds, compared with the other 2 antibiotics administered for the first 5 d of life. The results of the study are inconclusive as both desirable and undesirable effects of preventive early short-term antibiotic therapy were observed in turkeys, including normalization of ileal viscosity and cecal ammonia concentration (positive effect), and disruption in cecal SCFA production (negative effect).

Dramatic Suppression of Lipogenesis and No Increase in Beta-Oxidation Gene Expression Are among the Key Effects of Bergamot Flavonoids in Fatty Liver Disease.

Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed a RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes expressed in rat livers exposed for 14 weeks to different diets: standard, cafeteria (CAF) and CAF diet supplemented with 50 mg/kg of bergamot polyphenol fraction (BPF). CAF diet caused a strong upregulation of gluconeogenesis pathway (Gck, Pck2) and a moderate (>1.7 fold) induction of genes regulating lipogenesis (Srebf1, Pparg, Xbp1), lipid and cholesterol transport or lipolysis (Fabp3, Apoa1, Lpl) and inflammation (Il6, Il10, Tnf). However, only one ß-oxidation gene (Cpt1a) and a few autophagy genes were differentially expressed in CAF rats compared to controls. While most of these transcripts were significantly modulated by BPF, we observed a particularly potent effect on lipogenesis genes, like Acly, Acaca and Fasn, which were suppressed far below the mRNA levels of control livers as confirmed by alternative primers-based RT2-PCR analysis and western blotting. These effects were accompanied by downregulation of pro-inflammatory cytokines (Il6, Tnfa, and Il10) and diabetes-related genes. Few autophagy (Map1Lc3a, Dapk) and no ß-oxidation gene expression changes were observed compared to CAF group. In conclusion, chronic BPF supplementation efficiently prevents NAFLD by modulating hepatic energy metabolism and inflammation gene expression programs, with no effect on ß-oxidation, but profound suppression of de novo lipogenesis.

Prebiotics Together with Raspberry Polyphenolic Extract Mitigate the Development of Nonalcoholic Fatty Liver Diseases in Zucker Rats.

Previous studies suggested that dietary supplementation with prebiotic fructooligosaccharides (FOSs) and polyphenols could mitigate disorders related to the first stage of nonalcoholic fatty liver disease (NAFLD) induced by an obesogenic diet. Therefore, this experiment aimed to address whether the health-promoting potential of raspberry polyphenols together with FOSs can regulate advanced-stage NAFLD in Zucker rats genetically predisposed to develop obesity. The addition of FOSs and raspberry polyphenolic extract to the diet reduced liver fat accumulation and triglyceride, free fatty acid, and total cholesterol levels in the liver. The elevated GSH/GSSG ratio and reduced malondialdehyde content indicated that the liver antioxidant potential was considerably increased. The treatment also lowered the plasma aminotransferase and alkaline phosphatase activities and collagen type IV levels. Insulin levels were decreased, but glucose levels remained constant, indicating greater insulin sensitivity. These changes may result from the upregulation of FXR and AHR receptors in the liver, which are responsible for regulating lipid metabolism and glucose and bile acid synthesis. The reduced bile acid levels in the cecal contents confirmed the activation of liver mechanisms. In conclusion, dietary enrichment with FOSs and raspberry polyphenolic extract has sufficient health-promoting potential to regulate liver metabolism, oxidative stress, and inflammation related to NAFLD development in obese Zucker rats.

The Interaction of Dietary Pectin, Inulin, and Psyllium with Copper Nanoparticle Induced Changes to the Cardiovascular System.

We aimed to analyze how supplementation with a standard (recommended, 6.5 mg/kg) or enhanced (two-times higher, 13 mg/kg) dose of copper (Cu), in the form of nanoparticles (NPs) along with dietary intervention via the implementation of diverse types of fiber, affects the cardiovascular system in rats. Nine-week-old male Wistar Han rats (n/group = 10) received, for an additional 6 weeks, a controlled diet with cellulose as dietary fiber and ionic Cu (in the form of carbonate salt). The experimental groups received cellulose, pectin, inulin, and psyllium as dietary fiber, together with CuNPs (6.5 or 13 mg/kg diet). After the experimental feeding, samples of blood, hearts, and thoracic arteries were collected for further analysis. Compared to pectin, and under a standard dose of CuNPs, inulin and psyllium beneficially increased the antioxidant capacity of lipid- and water-soluble compounds in the blood, and decreased heart malondialdehyde. Moreover, pectin decreased heart catalase (CAT) and cyclooxygenase (COX)-2 in the aortic rings compared to inulin and psyllium under standard and enhanced doses of copper. When the dose of CuNPs was enhanced, inulin and psyllium potentiated vasodilation to acetylcholine by up-regulation of COX-2-derived vasodilator prostanoids compared to both cellulose and pectin, and this was modulated with selective inducible nitric oxide synthase (iNOS) inhibitor for psyllium only. Moreover, inulin decreased heart CAT compared to psyllium. Our results suggest that supplementation with dietary fiber may protect the vascular system against potentially harmful metal NPs by modulating the antioxidant mechanisms.

Dose-Related Regulatory Effect of Raspberry Polyphenolic Extract on Cecal Microbiota Activity, Lipid Metabolism and Inflammation in Rats Fed a Diet Rich in Saturated Fats.

The amount of berry polyphenols required to exert health-promoting effects seems to be difficult to achieve by fresh fruit ingestion, so polyphenol-rich extracts could be considered a dietary alternative. In the present study, laboratory rats were fed high-fat diets supplemented with 0.1 or 0.3% raspberry polyphenols from pomace, with the former dose reflecting the amount of polyphenols consumed with a glass of fresh raspberries. It was hypothesized that beneficial changes in blood and hepatic tissue related to lipid metabolism would accompany both treatments, but the health-promoting effect would be more noticeable with the higher dose of extract. This hypothesis was confirmed, and the high dose of raspberry polyphenols was better than the low dose extract in terms of decreased epididymal white adipose tissue weight, hepatic triglyceride content, PPARγ and SREBP-1c expression in the liver, and plasma IL-6 concentration, as well as increased acetic acid concentration in the cecal digesta. These effects might be partially associated with the enhanced content of ellagitannin and anthocyanin metabolites found in the blood plasma of rats administered the high dose of the extract. The results showed that this extract could be considered a dietary vehicle to provide an amount of raspberry polyphenols that could promote health.