Fructose-enriched Diet Research Articles

P097 SEXUAL DIMORPHISM IN A HYPERTENSIVE MODEL OF FRUCTOSE PLUS HIGH SALT DIET

High salt diet (HSD) and fructose are both consumed in excess and contributes to hypertension (HTN). Fructose is commonly used to sweeten soft drinks, and studies have linked soft drink consumption to salt-sensitive HTN. However, full mechanisms aren’t understood. Previous data indicates that an acute fructose-enriched diet (FED) increases Na/K/2Cl cotransporter (NKCC2) activity, promoting salt-sensitive HTN in rats; however, there is no research on long-term consumption. Here, our goal was to evaluate whether a FED, coupled to HSD, can induce HTN. Given the known sex-dependent differences in salt-sensitive HTN, we also hypothesized differences between male and female mice. Male and female C57BI/6 mice (10 weeks old, n=4-6) were treated with vehicle or fructose (10% in drinking water) plus HSD (4% in food) for 28 days. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography, and cardiac hypertrophy (morphometry). We performed an acute diuresis test using furosemide to inhibit NKCC2 (20 mg/kg bw, ip) at day 26, and then measured natriuresis (metabolic cages) for 2-hrs. All data are presented by mean standard deviation. Fructose+HSD increased SBP in male mice after 28 days (Veh=110.5±4.6 vs. Frucose+HSD=130.2±5.6 mmHg; p<0.01); in contrast, HTN was completely prevented in female mice (Veh=109.8±6.8 vs. Fructose+HSD=114.0±11.0 mmHg; ns). We did not observe changes in cardiac hypertrophy in either sex. We observed a significant decrease in natriuresis (∼20%) after furosemide injection in male mice (Veh=5.9±1.1 vs. Fructose+HSD=4.7±0.8 μEq/2 h/g bw; ns). Surprisingly, we observed an increase in natriuresis following furosemide injection in female mice (Veh=3.8±5.0 vs. Fructose+HSD= 7.7±2.7 μEq/2 h/g bw; p<0.01). We observed HTN in males following a FED combined with HSD, which was not associated with increased NKCC2 activation. In contrast, female mice showed a resistance to HTN, and yet an apparent increase in NKCC2 activity. This probably suggests a dysregulation of other transporters not evaluated in this work. Finally, we demonstrate that long-term FED, with HSD, induces HTN with a sexual dimorphic effect, apparently through differential renal sodium handling.

Spirulina (Arthrospira platensis) Improved Nonalcoholic Fatty Liver Disease Characteristics and Microbiota and Did Not Affect Organ Fibrosis Induced by a Fructose-Enriched Diet in Wistar Male Rats.

Spirulina (Arthrospira platensis) is reported to play a role in improving nonalcoholic fatty liver disease (NAFLD) and intestinal microbiota (IM). To study spirulina's effects in the improvement of NAFLD characteristics, IM, and pancreatic-renal lesions induced by a fructose-enriched diet, 40 Wistar healthy male rats, weighing 200-250 g, were randomly divided into four groups of 10, and each rat per group was assigned a diet of equal quantities (20 g/day) for 18 weeks. The first control group (CT) was fed a standardized diet, the second group received a 40% fructose-enriched diet (HFr), and the third (HFr-S5) and fourth groups (HFr-S10) were assigned the same diet composition as the second group but enriched with 5% and 10% spirulina, respectively. At week 18, the HFr-S10 group maintained its level of serum triglycerides and had the lowest liver fat between the groups. At the phylae and family level, and for the same period, the HFr-S10 group had the lowest increase in the Firmicutes/Bacteroidetes ratio and the Ruminococcaceae and the highest fecal alpha diversity compared to all other groups (p < 0.05). These findings suggest that at a 10% concentration, spirulina could be used in nutritional intervention to improve IM, fatty liver, metabolic, and inflammatory parameters associated with NAFLD.

Fennel seeds extract prevents fructose-induced cardiac dysfunction in a rat model of metabolic syndrome via targeting abdominal obesity, hyperuricemia and NF-κβ inflammatory pathway

BackgroundMetabolic syndrome (MetS) is commonly associated with increased risk of cardiac disease that affects a large number of world populations. ObjectiveThis research attempted to investigate the efficacy of fennel seeds extract (FSE) in preventing development of cardiac dysfunction in rats on fructose enriched diet for 3 months, as a model of MetS. Materials & methodsThirty adult Wistar male rats (160–170 g) were assigned into 5 groups including control, vehicle, FSE (200 mg/kg BW) and fructose (60%) fed rats with and without FSE. Following the last treatment, blood pressure, ECG and heart rate were measured. Next, blood and cardiac tissues were taken for biochemical and histological investigations. ResultsFeeding fructose exhibited characteristic features of MetS involving, hypertension, abnormal ECG, elevated heart rate, serum glucose, insulin, lipids and insulin resistance, accompanied by abdominal obesity, cardiac hypertrophy and hyperuricemia. Fructose fed rats also showed significant reduction in cardiac antioxidants (GSH, SOD, CAT) with elevation in oxidative stress indices (NADPH oxidase, O2.-, H2O2, MDA, PCO), NF-κβ, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), adhesion molecules (ICAM-1, VCAM-1) and serum cardiac biomarkers (AST, LDH, CK-MB, cTn-I). Histopathological changes evidenced by destruction of cardiac myofibrils, cytoplasmic vacuolization, and aggregation of inflammatory cells were also detected. Consumption of FSE showed high ability to alleviate fructose-induced hypertension, ECG abnormalities, cardiac hypertrophy, metabolic alterations, oxidative stress, inflammation and histological injury. ConclusionFindings could suggest FSE as a complementary supplement for preventing MetS and associated cardiac outcomes. However, well controlled clinical studies are still needed.

CD38 Inhibition Protects Fructose-Induced Toxicity in Primary Hepatocytes.

A fructose-enriched diet is thought to contribute to hepatic injury in developing non-alcoholic steatohepatitis (NASH). However, the cellular mechanism of fructose-induced hepatic damage remains poorly understood. This study aimed to determine whether fructose induces cell death in primary hepatocytes, and if so, to establish the underlying cellular mechanisms. Our results revealed that treatment with high fructose concentrations for 48 h induced mitochondria-mediated apoptotic death in mouse primary hepatocytes (MPHs). Endoplasmic reticulum stress responses were involved in fructose-induced death as the levels of phosho-eIF2α, phospho-C-Jun-N-terminal kinase (JNK), and C/EBP homologous protein (CHOP) increased, and a chemical chaperone tauroursodeoxycholic acid (TUDCA) prevented cell death. The impaired oxidation metabolism of fatty acids was also possibly involved in the fructose-induced toxicity as treatment with an AMP-activated kinase (AMPK) activator and a PPAR-α agonist significantly protected against fructose-induced death, while carnitine palmitoyl transferase I inhibitor exacerbated the toxicity. However, uric acid-mediated toxicity was not involved in fructose-induced death as uric acid was not toxic to MPHs, and the inhibition of xanthine oxidase (a key enzyme in uric acid synthesis) did not affect cell death. On the other hand, treatment with inhibitors of the nicotinamide adenine dinucleotide (NAD)+-consuming enzyme CD38 or CD38 gene knockdown significantly protected against fructose-induced toxicity in MPHs, and fructose treatment increased CD38 levels. These data suggest that CD38 upregulation plays a role in hepatic injury in the fructose-enriched diet-mediated NASH. Thus, CD38 inhibition may be a promising therapeutic strategy to prevent fructose-enriched diet-mediated NASH.

Gut microbiota induces hepatic steatosis by modulating the T cells balance in high fructose diet mice

Metabolic diseases are often associated with high fructose (HF) consumption. HF has also been found to alter the gut microbiota, which then favors the development of nonalcoholic fatty liver disease. However, the mechanisms underlying of the gut microbiota on this metabolic disturbance are yet to be determined. Thus, in this study, we further explored the effect the gut microbiota concerning the T cells balance in an HF diet mouse model. We fed mice 60% fructose-enriched diet for 12 weeks. At 4 weeks, HF diet did not affect the liver, but it caused injury to the intestine and adipose tissues. After 12 weeks, the lipid droplet aggregation was markedly increased in the liver of HF-fed mice. Further analysis of the gut microbial composition showed that HF decreased the Bacteroidetes/Firmicutes ratio and increased the levels of Blautia, Lachnoclostridium, and Oscillibacter. In addition, HF can increase the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the serum. T helper type 1 cells were significantly increased, and regulatory T(Treg) cells were markedly decreased in the mesenteric lymph nodes of the HF-fed mice. Furthermore, fecal microbiota transplantation alleviates systemic metabolic disorder by maintaining liver and intestinal immune homeostasis. Overall, our data indicated that intestinal structure injury and intestinal inflammation might be early, and liver inflammation and hepatic steatosis may be a subsequent effect following HF diets. Gut microbiota disorders impairing the intestinal barrier function and triggering immune homeostasis imbalance may be an importantly responsible for long-term HF diets induced hepatic steatosis.

Preparation, chemical characterization and determination of the antioxidant, cytotoxicity and therapeutic effects of gold nanoparticles green-synthesized by Calendula officinalis flower extract in diabetes-induced cardiac dysfunction in rat

• Preparation of mono-dispersed gold nanoparticles using the aqueous extract of Calendula officinalis. • Calendula officinalis acted as reducing and stabilizing agent. • COE@AuNPs shown good antioxidant properties. • The results shown therapeutic effects of COE@AuNPs on diabetes-induced cardiac dysfunction in rat. An ultrasound promoted bio-inspired synthesis of mono-dispersed Au nanoparticles (NPs) has been adopted in this article, templated over Calendula officinalis flower extract. The phytochemicals therein were explored as natural and green reducing as well as NP stabilizers. The as-synthesized bio-nanomaterial (COE@AuNPs) was characterized over FT-IR, UV–Vis spectroscopy, TEM, FE-SEM, EDX and XRD studies. Due to plant extract-based synthesis, the material was obtained as highly dispersed, semi-spherical particles of minuscule dimension (20–25 nm). In the in vivo condition, diabetes was induced by a fructose-enriched diet supplemented by streptozotocin. Half of the animals received COE@AuNPs by oral gavage. Compared to the animals receiving standard chow, serum fasting glucose level was increased and glucose tolerance was diminished in diabetic rats. COE@AuNPs affect significantly fasting hyperglycemia and glucose intolerance; also, it attenuated the diabetes-induced deterioration of cardiac output and cardiac work. Moreover, COE@AuNPs prevented the diabetes-induced increase in cardiac STAT3 phosphorylation. The results of this study indicated the therapeutic effects of COE@AuNPs the diabetes-induced cardiac dysfunction in rat.

A process systems Engineering approach to analysis of fructose consumption in the liver system and consequences for Non-Alcoholic fatty liver disease

Metabolic disturbances to the liver system can induce lipid deposition and subsequently cause non-alcoholic fatty liver disease (NAFLD). Increasing consumption of fructose has been proposed as a crucial risk component in the development of NAFLD.Three potential therapeutic targets in the network were explored using a composite model of liver function. Introducing a fructose enriched diet under insulin resistance conditions was simulated to evaluate the effectiveness of the model in novel therapy design. In vitro experiments were conducted on rat liver samples to assess the robustness of the model predictions.Synergistic application of all three interventional points in silico has been predicted as the most effective treatment to reduce lipid production under both moderate and severe insulin resistance conditions.This study demonstrates how we can use system models together with in vivo experiments to explore the behaviour of the liver system in response to fructose variation and use it to help identify possible drug targets.

Swimming exercise restores damaging effects of fructose-enriched diet on the liver in rats

Fructose-enriched diet (FED) is increasing worldwide. The study aims to investigate oxidative, histopathological, and immunohistochemical effects of fructose-enriched diet and swimming exercise on liver tissue in rats. Wistar rats were divided into 4 groups: Group I (Control), Group II (FED), Group III (FED+Exercise), and Group IV (Control+Exercise). MDA levels and enzyme activities of SOD and CAT were measured in liver tissue. Also, histopathological and immunohistochemical examinations (caspase-3, RANKL, TNF-α, and HSP-70) were performed on the liver tissue. MDA levels and SOD activities were found to be significantly higher in Group III compared to the other groups (p < 0.05). SOD activity was found to be lower in Group II compared to Group I (p = 0.035). CAT activities did not differ significantly between groups. While degeneration was noticed in Group II, normal tissue architecture was observed in other groups. Caspase-3, RANKL, and TNF-α expressions were higher in Group II than in the other groups, while HSP-70 expression was lower (p < 0.05). Fructose-enriched diet increases oxidative damage, degeneration, inflammation, and necrosis in the liver. In addition, a fructose-enriched diet is damaging to the liver by increasing the expressions of caspase 3, TNF-α, and RANKL and decreasing the expression of HSP-70. Swimming exercise largely restores these effects.

477-P: Vagal GLP-1–Mediated Reductions in Postprandial Lipids Are Sensitive to Fructose Feeding

Dyslipidemia is a common co-morbidity of insulin resistance, where chronic elevations in hepatic and intestinal lipoproteins are linked to cardiovascular disease. Postprandial production is regulated in-part by gut-derived hormones such as glucagon-like peptide (GLP) -1. Although degradation-resistant analogs of GLP-1 continue to work in diabetic individuals, none have examined whether GLP-1s endogenous neuroendocrine signalling pathways are affected by diet-induced dyslipidemia. Thus, we sought to test whether native GLP-1 could modulate postprandial lipids in a fructose-fed hamster model.Hamsters were fed either a chow or fructose-enriched (FF) diet for 14 days, then received a portal vein injection of either GLP-1 (7-36) or vehicle control to examine if they remained responsive to portal GLP-1. Separately, in hamsters fed either chow or a fat/fructose/cholesterol enriched (FFC) diet we performed nodose ganglia (NG) injections with GLP-1 (7-36) or vehicle. To recapitulate the loss of vagal GLP-1R signalling in the absence of dietary intervention we selectively deafferented GLP-1R containing NG neurons via injection of the cytotoxin saporin conjugated to exendin-4. After treatment, animals received a gavage of olive oil and an intraperitoneal injection of poloxamer to prevent lipoprotein clearance. Postprandial triglyceride-rich lipoproteins isolated via density ultracentrifugation were assessed via blood draws over a 6-hour period.Chow-fed hamsters saw significant reductions in post-prandial lipids after portal GLP-1 injection, whereas FF-fed hamsters were unaffected. Chow-fed hamsters were similarly responsive to GLP-1 (7-36) injection into the NG, displaying reduced postprandial lipids; however, FFC-fed hamsters showed no reduction in plasma lipids. Finally, selective deafferentation of NG GLP-1R-containing neurons caused significant rises in postprandial TG and TRL, underscoring the importance of GLP-1R insensitivity in states of metabolic disease. Disclosure S.S.Hoffman: None. D.C.Alvares: None. K.Adeli: None. Funding CIHR Foundation Grant

Effects of Pumpkin (Cucurbita pepo L.) Seed Protein on Blood Pressure, Plasma Lipids, Leptin, Adiponectin, and Oxidative Stress in Rats with Fructose-Induced Metabolic Syndrome

This study evaluates the potential effects of pumpkin seeds protein on blood pressure (BP), plasma adiponectin, leptin levels, and oxidative stress in rats with fructose-induced metabolic syndrome. Twenty four male Wistar albino rats were divided into four groups and fed a 20% casein diet, 20% casein diet supplemented with pumpkin protein, 20% casein diet with 64% D-fructose, or 20% casein diet with pumpkin protein and 64% D-fructose for 8 weeks. Contin-uous fructose feeding induced an increase in plasma insulin/glucose ratio, BP, insulin and glucose, aspartate aminotrans-ferase, alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, urea, and uric acid levels, and a decrease in the liver and muscle glycogen stores. In addition, elevated levels of total cholesterol (TC), triglycerides (TG), and leptin and lowered adiponectin levels were observed in rats fed a fructose-enriched diet. These groups also exhibited lower plasma levels of ascorbic acid and glutathione, higher thiobarbituric acid-reactive substances, hydroperoxide, carbonyl, and nitric oxide in both the liver and kidneys than rats fed the control diet. Interestingly, pumpkin seed protein treatment significantly counteracted alterations induced by fructose improving glucose, insulin, BP, TG, TC, ALT, and ALP levels, increasing liver and muscle glycogen stores, adiponectin level, and adiponectin/leptin ratio, and reducing plasma leptin lev-els. In addition, rats fed pumpkin protein with a high-fructose diet improved oxidative stress in the liver and kidneys. In conclusion, proteins from Cucurbita pepo L. seeds effectively improve metabolic parameters and protect against oxidative stress induced by a high-fructose diet.

Evaluation of indicators of carbohydrate and lipid metabolism in rats depending on the type of high-calorie diet

BACKGROUND: Recently, there has been an increase in the number of cardiovascular diseases and mortality rates among the population. This may be due to a violation of metabolic processes in the body, in particular lipid and carbohydrate metabolism, caused by an unbalanced high-calorie diet.PURPOSE: To study and compare the main indicators of carbohydrate and lipid metabolism in a fructose-fortified diet and a diet with a high fat content under experimental conditions.MATERIALS AND METHODS: The study was carried out on outbred white rats, males, which were divided into 3 groups — a control group and two experimental ones, 15 individuals in each. The rats of the first experimental group were kept on a high-fat diet, the second experimental group was assigned a fructose-enriched diet for 35 days. The control group was on a balanced diet. We studied the changes in the parameters of carbohydrate (glucose, insulin, insulin resistance indices) and lipid (cholesterol-, high- and low-density lipoproteins, triglycerides) metabolism on the 21st, 35th and 60th days of the experiment. The results were statistically processed using the Mann-Whitney test. The study design is retrospective.RESULTS: During the experiment, an increase in the content of glucose, insulin, and lipid metabolism parameters was observed in the experimental groups. Moreover, the content of glucose and insulin in a fructose-fortified diet increased by 18.7% (p = 0,009), 22.2% (p = 0,076), 21.5% (p = 0,009) and 50% (p = 0,009), 62.5% (p = 0,009), 106.3% (p = 0,009) over the days of the experiment, respectively. The increase in lipid metabolism was more pronounced in the experimental group, which had an increased fat content in the diet, already in the first time period of the experiment: cholesterol — by 80,8% (p = 0,009), low-density lipoproteins — by 100% (p = 0,009), triglycerides — by 120% (p = 0,009), high-density lipoproteins — by 60.9% (p = 0,009).CONCLUSION: The experimental data obtained show changes in lipid and carbohydrate metabolism due to increased consumption of fats and fructose.

FRUCTOSE DIET INDUCES A METABOLIC REPROGRAMMING TO ENHANCE TUMOR AGGRESSIVENESS

HCC is one of the main causes of cancer-related death worldwide and has third place in mortality. One of the main risk factors is metabolic-associated fatty liver disease (MAFLD), having hepatic steatosis, and related metabolic disorders. Mexican population has the highest obesity rate in both children and adults, and the consumption of hypercaloric diets has been related to that. Also, Mexico is in the top five countries with a higher fructose-enriched diet consumption and has been proved already the relation between fructose consumption and MAFLD. Likewise, fructose has been related to metabolic rewiring in transformed cells, enhancing aggressiveness and survival. To analyze fructose role on aggressiveness promotion of HCC cells. We used C57Bl/6J mice strain (both sex) with a high Fructose diet (Fru) (33% of fructose in the drinking water, ad libitum ). Fru supplementation started with 15 days-old mice, two days after DEN was injected (10 μg/Kg, i.p), and the treatment was ended 8 months later. The UAM ethics committee approved the protocol. In vitro studies were carried out with the Huh-7 HCC cell line and we evaluated metabolic and biochemical parameters. Tissue samples were analyzed by H&E. We observed that the fructose-enriched diet group mice presented fat accumulation in the hepatocytes and also areas with a greater inflammatory infiltrate (Fru). Mice in the fructose-enriched diet + DEN (Fru/HCC) group showed a marked difference between the tumor area and the surrounding tissue and an increase in the number of bile ducts, indicating liver tissue damage. Also, we analyzed the protein content of some lipogenic enzymes and noticed an increment in fatty acid synthase (Fasn) in Fru and Fru/HCC. Due to that, we analyzed if Fru treatment was inducing metabolic rewiring in transformed cells. We obtained metabolic changes in fructose-treated cells, reducing the glycolytic pathway and the traditional Warburg effect. Then we evaluated if the Huh-7 under a Fru treatment was more dependent on mitochondria or glycolysis ATP generation. We observed a reduction in proliferation under oligomycin treatment vs . 2-DG treatment. At least, we evaluated the pentose phosphate pathway (PPP) under a Fru treatment and obtained a higher glucose-6-phosphate dehydrogenase (G-6-P DH) activity with Fru vs. only glucose (Glc). Also, G-6-P DH had a more efficient activity in the presence of Fru because the time to reach the Vmax is lower vs . Glc. Fructose induces a metabolic rewiring in cancer cells to enhance ATP production, NADPH, and nucleotides to sustain the active lipid synthesis and proliferation. The fructose-enriched diets promote an aberrant lipogenic phenotype enhancing tumor aggressiveness. Conacyt, Froteras de la Ciencia 1320. The authors declare that there is no conflict of interest.

Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats.

Introduction: Obesity and related metabolic disturbances are frequently related to modern lifestyle and are characterized by excessive fructose intake. Visceral adipose tissue (VAT) inflammation has a central role in the development of insulin resistance, type 2 diabetes (T2D), and metabolic syndrome. Since sex-related differences in susceptibility and progression of metabolic disorders are not yet fully understood, our aim was to examine inflammation and insulin signaling in VAT of fructose-fed female and male adult rats.Methods: We analyzed effects of 9-week 10% fructose-enriched diet on energy intake, VAT mass and histology, and systemic insulin sensitivity. VAT insulin signaling and markers of VAT inflammation, and antioxidative defense status were also evaluated.Results: The fructose diet had no effect on VAT mass and systemic insulin signaling in the female and male rats, while it raised plasma uric acid, increased PPARγ level in the VAT, and initiated the development of a distinctive population of small adipocytes in the females. Also, adipose tissue insulin resistance, evidenced by increased PTP1B and insulin receptor substrate 1 (IRS1) inhibitory phosphorylation and decreased Akt activity, was detected. In addition, fructose stimulated the nuclear accumulation of NFκB, increased expression of proinflammatory cytokines (IL-1β, IL-6, and TNFα), and protein level of macrophage marker F4/80, superoxide dismutase 1, and glutathione reductase. In contrast to the females, the fructose diet had no effect on plasma uric acid and VAT inflammation in the male rats, but less prominent alterations in VAT insulin signaling were observed.Conclusion: Even though dietary fructose did not elicit changes in energy intake and led to obesity in the females, it initiated the proliferation of small-sized adipocytes capable of storing fats further. In contrast to the males, this state of VAT was accompanied with enhanced inflammation, which most likely contributed to the development of insulin resistance. The observed distinction could possibly originate from sex-related differences in uric acid metabolism. Our results suggest that VAT inflammation could precede obesity and start even before the measurable increase in VAT mass, making it a silent risk factor for the development of T2D. Our results emphasize that adipose tissue dysfunction, rather than its simple enlargement, could significantly contribute to the onset and development of obesity and related metabolic disorders.

Dynamics of Pro- and Anti-inflammatory Cytokines in Experimental Animals with Non-alcoholic Fatty Liver Disease Under Conditions of Hypobaric Hypoxia

AIM: The aim of the study was to study the level of pro- and anti-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin 4 (IL-4), on a model of non-alcoholic fatty liver disease (NAFLD) in experimental animals under conditions of low mountains and hypobaric hypoxia. METHODS: The study was carried out on 180 male Wistar rats, which were divided into control and experimental groups. The rats of the control group were on a standard diet. NAFLD was modeled by keeping animals on a diet (Ackermann et al., 2005) rich in fructose and fat in conditions of low mountains and hypobaric hypoxia (in a pressure chamber 6000 m above sea level) for 35 and 70 days. Total cholesterol (TC) and lipid spectrum, pro- and anti-inflammatory cytokines were determined in all groups of animals. RESULTS: The activity of pro- and anti-inflammatory cytokines in the main group during the rise of animals in the pressure chamber increased statistically significantly on the 35th day in comparison with the low-altitude group by more than 2 times, and on the 70th day of staying at the high-altitude did not have convincing differences from the low-altitude group. The cytokine index (TNF-α/IL-4) of animals in conditions of hypobaric hypoxia on a fructose enriched diet increased by more than 1.5 times after 5 weeks, staying at an altitude for 10 weeks led to a decrease of TNF-α/IL-4 in relation to the low-mountain group, in which the opposite picture was observed - a tendency towards an increase in TNF-α/IL-4. IL-4 and TNF-α _levels were statistically significantly correlated with lipid metabolism disorders. CONCLUSION: NAFLD in animals on a special diet enriched with fructose under conditions of hypobaric hypoxia leads to deeper disturbances in the system of pro- and anti-inflammatory cytokines and the lipid spectrum.

High fructose corn syrup supplementation progressively increased serum adenosine and inosine: Inosine raising blood pressure and heart rate in rats

High fructose corn syrup (HFCS) over-consumption underlies the obesity worldwide epidemics. Hepatic fructose metabolism includes fructolysis, lipogenesis, and purines degradation to uric acid. The aim of this study was to evaluate HFCS long-term effects on serum and hepatic adenosine (Ado) and inosine (Ino), as well as in vivo Ino effects on cardiovascular function. Fed male Wistar rats were subjected to 30% HFCS-enriched drinking water for five months (n = 15); every month, nucleosides were determined in serum and in isolated liver perfusate. Three months-old male naive Wistar rats were pithed and cannulated to record blood pressure and heart rate after Ino administration (n = 3). Rats consuming HFCS increased both Ado and Ino progressively in serum and livers’ perfusate; Ino increased cardiovascular function. The progressive Ado and Ino hepatic release by fructose-enriched diet suggests their contribution to raise glycemia through their gluconeogenic activation, and a higher serum Ino concentration might be related to increase in arterial blood pressure.

Highbush Blueberry (Vaccinium corymbosum L.) Leaves Extract and Its Modified Arginine Preparation for the Management of Metabolic Syndrome-Chemical Analysis and Bioactivity in Rat Model.

Growing blueberry (Vaccinium corymbosum L., Highbush blueberry) as a berry crop is developing dynamically, especially in warm temperate, subtropical, and tropical regions of the world. When blueberry is cultivated on plantations, the bushes are pruned annually, and tons of leaves become waste. Thus, the aim of the present study was to create a preparation from blueberry leaves, study their chemical composition and determine their potential as a dietary supplement for the prophylactic and correction of the metabolic syndrome. Several schemes for obtaining extracts from blueberry leaves have been developed, including one with addition of arginine. A total of 18 phenolic substances were identified and quantified in the extracts by TLC and HPLC methods. Chlorogenic acid, hyperoside, and rutin were shown to be dominating constituents. Quantitative determination of hydroxycinnamic acid derivatives, flavonoids and other phenolics in the extracts was performed by spectrophotometric method. The extracts administration led to a significant decrease in the level of glucose, insulin and triacylglycerols in blood serum of adult mature inbred rats with insulin resistance induced by the fructose-enriched diet. The most promising one was the extract modified with arginine. The determined hypoglycemic and hypolipidemic activity of chemically standardized extracts from highbush blueberry leaves indicate the potential of this crop residue in utilization as a dietary supplement recommended in prevention of ailments associated with metabolic syndrome.

Stellaria media tea protects against diabetes-induced cardiac dysfunction in rats without affecting glucose tolerance

Background and aimCommon chickweed (Stellaria media) tea has traditionally been applied for treatment of various metabolic diseases including diabetes in folk medicine; however, experimental evidence to support this practice is lacking. Therefore, we aimed to assess the effect of Stellaria media tea on glucose homeostasis and cardiac performance in a rat model of diabetes. Experimental procedureHot water extract of Stellaria media herb were analyzed and used in this study, where diabetes was induced by fructose-enriched diet supplemented with a single injection of streptozotocin. Half of the animals received Stellaria media tea (100 mg/kg) by oral gavage. At the end of the 20-week experimental period, blood samples were collected and isolated working heart perfusions were performed. Results and conclusionCompared to the animals receiving standard chow, serum fasting glucose level was increased and glucose tolerance was diminished in diabetic rats. Stellaria media tea did not affect significantly fasting hyperglycemia and glucose intolerance; however, it attenuated diabetes-induced deterioration of cardiac output and cardiac work. Analysis of the chemical composition of Stellaria media tea suggested the presence of rutin and various apigenin glycosides which have been reported to alleviate diabetic cardiomyopathy. Moreover, Stellaria media prevented diabetes-induced increase in cardiac STAT3 phosphorylation. We demonstrated for the first time that Stellaria media tea may beneficially affect cardiac dysfunction induced by diabetes without improvement of glucose homeostasis. Rutin and/or apigenin glycosides as well as modulation of STAT3 signaling may be implicated in the protection of Stellaria media tea against diabetic cardiomyopathy.

Decreased Glucocorticoid Signaling Potentiates Lipid-Induced Inflammation and Contributes to Insulin Resistance in the Skeletal Muscle of Fructose-Fed Male Rats Exposed to Stress.

The modern lifestyle brings both excessive fructose consumption and daily exposure to stress which could lead to metabolic disturbances and type 2 diabetes. Muscles are important points of glucose and lipid metabolism, with a crucial role in the maintenance of systemic energy homeostasis. We investigated whether 9-week fructose-enriched diet, with and without exposure to 4-week unpredictable stress, disturbs insulin signaling in the skeletal muscle of male rats and evaluated potential contributory roles of muscle lipid metabolism, glucocorticoid signaling and inflammation. The combination of fructose-enriched diet and stress increased peroxisome proliferator-activated receptors-α and -δ and stimulated lipid uptake, lipolysis and β-oxidation in the muscle of fructose-fed stressed rats. Combination of treatment also decreased systemic insulin sensitivity judged by lower R-QUICKI, and lowered muscle protein content and stimulatory phosphorylations of insulin receptor supstrate-1 and Akt, as well as the level of 11β-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor. At the same time, increased levels of protein tyrosine phosphatase-1B, nuclear factor-κB, tumor necrosis factor-α, were observed in the muscle of fructose-fed stressed rats. Based on these results, we propose that decreased glucocorticoid signaling in the skeletal muscle can make a setting for lipid-induced inflammation and the development of insulin resistance in fructose-fed stressed rats.

Macrophage migration inhibitory factor deficiency aggravates effects of fructose-enriched diet on lipid metabolism in the mouse liver.

Dietary fructose can disturb hepatic lipid metabolism in a way that leads to lipid accumulation and steatosis, which is often accompanied with low-grade inflammation. The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with important role not only in the regulation of inflammation, but also in the modulation of energy metabolism in the liver. Thus, the aim of this study was to investigate the role of Mif deficiency in fructose-induced disturbances of hepatic lipid metabolism and ectopic lipid accumulation. Wild type (WT) and Mif deficient (MIF-/- ) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on hepatic lipid metabolism (both lipogenesis and β-oxidation) and histology, inflammatory status and glucocorticoid receptor (GR) signaling. The results showed fructose-induced elevation of lipogenic genes (fatty acid synthase (Fas) and stearoyl-CoA desaturase-1 (Scd1) and transcriptional lipogenic regulators (liver X receptor (LXR), sterol regulatory element binding protein 1c (SREBP1c), and carbohydrate response element-binding protein (ChREBP)). However, microvesicular fatty changes, accompanied with enhanced inflammation, were observable only in fructose-fed Mif deficient animals, and were most likely result of GR activation and facilitated uptake and decreased β-oxidation of FFA, as evidenced by elevated protein level of fatty acid translocase (FAT/CD36) and decreased carnitine palmitoyl transferase 1 (CPT1) level. In conclusion, the results show that Mif deficiency aggravates the effects of energy-rich fructose diet on hepatic lipid accumulation, most likely through enhanced inflammation and activation of GR signaling pathway.

Lifestyle-Induced Redox-Sensitive Alterations: Cross-Talk among the RAAS, Antioxidant/Inflammatory Status, and Hypertension.

The development and progression of hypertension are closely linked to an unhealthy lifestyle; however, its underlying mechanisms are not fully elucidated. Our aim was to assess the effects of diet and exercise on the elements of the renin–angiotensin–aldosterone system (RAAS), redox-sensitive parameters, and the expression of the vascular tone regulator endothelial nitric oxide synthase (eNOS). Male control Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats were randomized based on the type of diet (standard chow, high-fat diet: HT, and fructose-enriched diet: HF) and exercise (voluntary wheel-running exercise or lack of exercise). After 12 weeks of experimental period, the concentrations of the RAAS elements, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) concentrations, levels of superoxide dismutase (SOD) and glutathione (GSH), and expressions of extracellular signal-regulated kinase1/2 (ERK1/2) and phosphorylated ERK1/2 as well as eNOS were measured in the cardiac tissue of WKY and SHRSP rats. We found that the RAAS elements were overactivated under hypertension and were further elevated by HT or HF diet, while HT and HF diet enhanced MPO and TNF-α parameters as well as the expression of pERK1/2; SOD, GSH, and eNOS levels were decreased. These changes occurred in WKKY rats and reached the statistically significant level in SHRSP animals. 12 weeks of exercise compensated the adverse effects of HT and HF via alleviating the concentrations of the RAAS elements and inflammatory markers as well as increasing of antioxidants. Our findings prove that SHRSP rats are more vulnerable to lifestyle changes. Both the type of diet and exercise, as a nonpharmacological therapeutic tool, can have a significant impact on the progression of hypertension.