Fructose Group Research Articles

Fructose threshold for inducing organ damage in a rat model of nonalcoholic fatty liver disease

A fructose-enriched diet has been shown to be associated with an increase in fatty infiltration of liver, kidney, and pancreas. Our objective was to determine the concentration threshold at which a fructose-enriched diet induces damage in these organs. We hypothesized that a 20% fructose-enriched diet will induce steatosis or histopathological changes in the kidneys or pancreas. In this study, 40 Wistar male rats were randomly divided into 4 groups of 10, and each group was assigned a diet of equal quantity (15 g/rat) but of varying fructose amount. The first group (control group) was fed a standardized diet. The second and third groups were fed 10% and 20% fructose-enriched diets, respectively, whereas the fourth group was fed a high-fructose diet (30% fructose). At week 16, the 30% fructose group had the highest percentage of fat-enriched cells (10%) and a significant decrease in adiponectin as compared with week 1 (P < .05). Twenty percent of this group developed interstitial fibrosis, but none presented changes in the pancreatic islet structure or fibrosis. The 10% fructose group showed the absence of perisinusoidal and interstitial fibrosis, whereas these were present in the 20% fructose group, but neither group showed significant steatosis (5%) or pancreatic damage. The results suggest that a 20% fructose-enriched diet could be considered as the threshold for inducing kidney and liver damage in the rat. Nutritional interventions to reduce fructose to less than 20% of the total energy intake should be considered to prevent metabolic risks and organ damage.

Intra-Renal Angiotensin Levels Are Increased in High-Fructose Fed Rats in the Extracorporeal Renal Perfusion Model.

Overconsumption of fructose leads to metabolic syndrome as a result of hypertension, insulin resistance, and hyperlipidemia. In this study, the renal function of animals submitted to high fructose intake was analyzed from weaning to adulthood using in vivo and ex vivo methods, being compared with a normal control group. We investigated in ex vivo model of the role of the renin Angiotensin system (RAS) in the kidney. The use of perfused kidney from animals submitted to 8-week fructose treatment showed that high fructose intake caused metabolic and cardiovascular alterations that were consistent with other studies. Moreover, the isolated perfused kidneys obtained from rats under high fructose diet showed a 33% increase in renal perfusion pressure throughout the experimental period due to increased renal vascular resistance and a progressive fall in the glomerular filtration rate, which reached a maximum of 64% decrease. Analysis of RAS peptides in the high fructose group showed a threefold increase in the renal concentrations of angiotensin I (Ang I) and a twofold increase in angiotensin II (Ang II) levels, whereas no change in angiotensin 1-7 (Ang 1-7) was observed when compared with the control animals. We did not detect changes in angiotensin converting enzyme (ACE) activity in renal tissues, but there is a tendency to decrease. These observations suggest that there are alternative ways of producing Ang II in this model. Chymase the enzyme responsible for Ang II formation direct from Ang I was increased in renal tissues in the fructose group, confirming the alternative pathway for the formation of this peptide. Neprilysin (NEP) the Ang 1-7 forming showed a significant decrease in activity in the fructose vs. control group, and a tendency of reduction in ACE2 activity. Thus, these results suggest that the Ang 1-7 vasodilator peptide formation is impaired in this model contributing with the increase of blood pressure. In summary, rats fed high fructose affect renal RAS, which may contribute to several deleterious effects of fructose on the kidneys and consequently an increase in blood pressure.

New insights into fumonisin production and virulence of Fusarium proliferatum underlying different carbon sources

Fusarium proliferatum is not only a dangerous plant pathogen but also produces various mycotoxins. The aim of this study was to investigate the influences of different carbon sources on fumonisins (FB1 and FB2) production and fungal virulence of F. proliferatum. The use of sucrose as the sole carbon source significantly increased the production of fumonisins in F. proliferatum in comparison to fructose. While F. proliferatum showed the stronger ability to infect banana fruit in the fructose group than the sucrose group, which was further investigated by scanning electron microscope (SEM) observations. Differentially expressed genes (DEGs) between the two groups were revealed by Illumina sequencing, including 1293 up-regulated and 907 down-regulated genes. Among them, many important genes were involved in carbohydrate metabolism, including starch and sucrose, and fructose and mannose metabolism. Additionally, the homologous FUM genes in association with fumonisins biosynthesis, including FUM1, FUM8 and TUM15, were up-regulated on sucrose compared with fructose. Furthermore, F. proliferatum cultured on fructose source compared with sucrose source showed higher virulence for colonizing green and mature bananas by up-regulating CWDE (cell wall-degrading enzyme)-related genes, which was further confirmed by qRT-PCR. Hence, the results obtained by RNA-Seq, HPLC-MS/MS and virulence experiments elucidated partially that the use of fructose as the sole carbon source can facilitate the fungal pathogenicity, but depress fumonisins production in F. proliferatum.

Potential effect of maternal dietary sucrose or fructose syrup on CD36, leptin, and ghrelin-mediated fetal programming of obesity

The influence of HFCS (high fructose corn syrup – free fructose) and sucrose (bound fructose) on fetal appetite signals is unknown. This study aimed to determine the effects of HFCS or sucrose on the peptide-mediated appetite regulation in fetal programming of obesity. Sprague Dawley female rats were administered feed and plain water (control) or water containing maltodextrin (vehicle), sucrose, fructose, or HFCS (20%, w/v) for 12 weeks before mating and throughout pregnancy and lactation (ndams = 31; npups = 207). Maternal chow-feed consumption in the HFCS and sucrose groups and sugar-added drink consumption in the HFCS group were higher compared to the vehicle and control groups (P < 0.05). The total body fat accumulated in sucrose, fructose, and HFCS groups in dams and pups was higher than those in the vehicle and control groups (P < 0.05). The HFCS groups showed lower plasma leptin levels and higher ghrelin levels. Soluble CD36 levels in plasma and tongue samples were high in HFCS groups of dams and pups (P < 0.05). Rather than bound fructose, the free fructose from the maternal diet contributes to the programming of obesity through the disruption of leptin, ghrelin, and CD36 expression involved in appetite regulation.

MODULATION WAY CLASSICAL AND ALTERNATIVES OF RENIN ANGIOTENSIN SYSTEM (RAS) IN MESANGIAL CELLS AFTER EXPOSURE TO FRUCTOSE.

BackgroundOur group demonstrated previously that rats subjected to a high fructose diet showed increased activity of kidney ACE. In order to understand the effect of fructose in the forming process of angiotensin II (Ang II) and angiotensin 1–7 (Ang1–7) affecting the levels of these effectors, the aim of this study was to evaluate the activities of the RAS enzymes responsible for the formation of Ang1–7 and Ang II of immortalized human mesangial cells (IMCH)exposed to low and high concentration of fructose.MethodsIMCH were divided into control (low glucose medium), Fructose 5 mM(medium + 5 mM Fructose) and Fructose 30mM(medium + 30 mM Fructose) groups. The enzymatic activity of ACE, chymase, cathepsin D, Neutral Endopeptidase (NEP) and ACE2 were evaluated using Z‐Phe‐His‐Leu, Abz‐AIKFFSAQ‐EDDnp, Abz‐AIAFFSRQ‐EDDnp, Abz(d)‐Arg‐Gly‐Leu, Mca‐APK (DNP) as substrates, respectively. Data were analyzed using ANOVA one way.ResultsAmong the AngII forming enzymes, fructose decreased ACE activity (CG:0,044±0,01 vs.F5:0,016±0,004* vs. F30:0,008±0,002* mU/mg protein) in cell lysate. Both fructose concentrations increased chymase (CG:0,85±0,03 vs. F5:1,07±0,07* vs. F30:0,99±0,05* nM/min/mL) in the culture medium. No effect was observed on the activity of cathepsin D. When evaluating the activities of peptidases forming Ang‐1–7, NEP activity was decreased in lysate cells in F30 group and decreased in F5 group in culture medium. We did not detect differences in ACE2 activity.ConclusionThe results suggest fructose modulates renal and systemic RAS in IMCH acting in the classical and alternative pathways of Ang II formation. Additionally, this sugar was able to decrease NEP activity, forming Ang‐1–7. Quantitation of angiotensin remains necessary to better understand how the end effector is available in IMCH and to evaluate possible effects on glomerular physiology.Support or Funding InformationCapesThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The effects of glucose and fructose on body weight and some biochemical parameters in rats

Objective: Dietary fructose from added sugar as high fructose corn syrup may causes major risks in obesity, hyperlipidemia, cardiovascular diseases, hyperuricemia and fatty liver. The aim of this study was to investigate and compare the effects of high fructose and high glucose intake on body weight and some biochemical parameters in rats. Subject and methods: The study was conducted on adult, 32 Wistar albino male rats (300-350 g weeks) which fed with standard laboratory chow. In each group, 8 rats was selected randomly and which was be composed four groups. The rats in each group, in addition to standard meal, different amount of glucose and fructose containing solutions (10% and 30% glucose-fed group, 10% and 30% fructose-fed group) was given by oral gavage for 6 weeks. At baseline and after 6 weeks total cholesterol, VLDL-cholesterol, triglycerides, uric acid, AST and ALT as biochemical parameters and liver histopathological examination of rats were determined. Body weight of the rats was evaluated every week. Results:The 30% fructose group caused higher AST levels according to 10% glucose group, 30% glucose group and 10% fructose group. At the end of 6 weeks, the mean body weight in the fructose-fed groups was higher than the glucose-fed groups (p>0.05). No statistically significant difference between rat groups’ portal inflammation rates were found and the moderate and severe ballooning were observed in 30% fructose rats (p<0.05). Conclusions: As a result, dietary fructose from added sugar as high fructose corn syrup may causes major metabolic disorders.

Value of absorbable hemostat textile as submucosal injection of endoscopic submucosal dissection

Objective To evaluate the application value of absorbable hemostat textile as submucosal injection of endoscopic submucosal dissection (ESD). Methods Twelve New Zealand rabbits were injected with absorbable hemostat textile solution, glycerol fructose and normal saline. The uplift effect was measured after injection. Simulated ESD was performed in the rabbit stomach and bleeding amount was measured. The injection site was pathologically examined at 30 minutes after the soluble hemostat textile and normal saline were injected. Fifteen pigs were injected with absorbable hemostat textile at two locations of 20-30 cm from the anus, and injected normal saline at another two locations of 20-30 cm from the anus. One site was performed simulated ESD and the other was not. Fifteen simulated ESD were performed in the soluble hemostatic group and the normal saline group, respectively. Operation time was recorded and difference in wound healing was compared between the two groups. Results In the uplift experiment, the absorbable hemostat textile group had higher uplift height (4.3±1.4 mm, 4.1±1.9 mm, 3.8±0.7 mm, 3.3±0.9 mm, respectively) at 0 min, 10 min, 20 min, 30 min than that of the glycerol fructose group (4.3±2.2 mm, 4.1±2.0 mm, 3.6±1.4 mm, 3.2±0.8 mm, respectively, P 0.05). In the bleeding experiment, the bleeding amount of absorbable hemostat textile group was significantly less than that of the glycerol fructose group (0.36±0.07 mL VS 0.42±0.06 mL, P<0.05); the bleeding amount of glycerol fructose group was significantly lower than that of the normal saline group (0.42±0.06 mL VS 0.55±0.07 mL, P<0.05). There was no obvious tissue necrosis and other adverse complications in the absorbable hemostat textile group and the normal saline group. In simulated ESD experiment, complete resection rate of the absorbable hemostat textile group was higher than that of the normal saline group [86.7%(13/15) VS 46.7%(7/15), P<0.05], and mean operation time of the absorbable hemostat textile group was less than that of the normal saline group (3.2±0.3 min VS 3.8±0.5 min, P<0.05). No hemorrhage, perforations or other related adverse events occurred in non-ESD lesions. Conclusion Absorbable hemostat textile is safe and effective as submucosal injection of ESD. Key words: Models, animal; Endoscopic submucosal dissection; Absorbable hemostat textile; Wound repair; Submucosal fluid cushion

Açai improves non-alcoholic fatty liver disease (NAFLD) induced by fructose.

the excessive consumption of fructose can cause liver damage, characteristic of non-alcoholic fatty liver disease (NAFLD) associated with changes in lipid metabolism and antioxidant defenses. Açai, the fruit of Euterpe oleraceaMart., has demonstrated numerous biological activities, including anti-inflammatory, antioxidant, and lipid metabolism modulating action. we evaluated the benefits of açai supplementation on liver damage caused by replacing starch with fructose in rats. thirty male Fischerrats were divided into two groups, the control group (C, 10 animals), which consumed a standard diet (AIN-93M), and the fructose (F, 20 animals) group, which consumed a diet containing 60% of fructose. After eight weeks, 10 animals from the fructose group received 2% of lyophilized açai, and were called the açai fructose group (FA). The animals were fed ad libitumwith these diets for another ten weeks. Serum, hepatic and fecal lipid profile, antioxidant enzymes and carbonylated protein were assessed and histopathological characterization of the liver was performed. açai promoted the reduction of ALT activity in relation to the fructose group (F), reduced alkaline phosphatase to a level similar to that of the control group (C) in relation to the fructose group (F), and reduced catalase activity. The fruit also increased the ratio of total/oxidized glutathione (GSH/GSSG) and reduced the degree of macrovesicular steatosis and the number of inflammatory cells. the replacement of starch by fructose during this period was effective in promoting NAFLD. Açai showed attenuating effects on some markers of hepatic steatosis and inflammation.

Alteration of Renal Natriuretic Systems Is Associated with the Development of Hypertension and Precedes the Presence of Renal Damage in a Model of Metabolic Syndrome

Objective: The aim of this study was to determine the presence of alterations in the natriuretic systems of atrial natriuretic peptide and renal dopamine in a model of metabolic syndrome induced by fructose overload and to associate them with changes in systolic blood pressure, renal function, Na+/K+-ATPase status and microalbuminuria. Methods: Male Sprague-Dawley rats were divided into control (C) and fructose (F) groups receiving drinking water or a fructose solution (10% W/V), respectively, for 4, 8 and 12 weeks. L-dopa and dopamine, sodium, creatinine and albumin were measured in urine and ANP, insulin, sodium and creatinine in plasma. Systolic blood pressure was measured by indirect method and the renal activity and expression of Na+/K+-ATPase as well as the renal expression of A- and C-type natriuretic peptide receptors were assessed. Results: Fructose overload was associated with a significant increase in insulinemia and systolic blood pressure levels and a decrease in urinary sodium excretion since week 4. A significant increase in L-dopa excretion and a decrease in dopamine excretion (increased urinary L-dopa/dopamine ratio) due to fructose overload were observed since week 4 with a decrease in plasma atrial natriuretic peptide at weeks 8 and 12. These changes were accompanied by increased activity and expression of Na+/ K+-ATPase, decreased A-type natriuretic peptide receptor and increased C-type natriuretic peptide receptor expression. Microalbuminuria was observed at week 12 of fructose overload. 1

Fructose-Induced Cognitive Dysfunction is Associated with Increased Oxidative Stress in the Rat Brains

High fructose consumption is a risk factor for diabetes. Type 2 diabetes is associated with cognitive and memory impairment. To determine if fructose intake might affect memory function independently of diabetes development, we investigated the effects of monosaccharides on memory in prediabetic state. We examined whether 2.5% apple juice solution could influence cognitive function in salt-sensitive Dahl rats using passive avoidance methods. Furthermore, we examined the role of monosaccharides intake in cognitive function and oxidative stress in the brain. Four-week consumption of either apple juice or 2.5% fructose did not affect the blood glucose concentrations; however, apple juice, but not fructose, significantly decreased cognitive function compared with that of control rats given water. Second, Wistar rats aged 4 weeks were assigned to four groups given water, or 1.25% glucose, or fructose, or galactose solutions for 11 weeks. The fructose group had only slightly higher blood glucose concentrations than the control group. However, memory function engraved at age of 7 weeks and evaluated for 8 weeks in a passive avoidance test, was significantly decreased in the fructose and galactose groups compared with those in the glucose group. Oxidative stress in the brain, assessed by the tissue malondialdehyde (MDA) content, was significantly increased in the fructose group compared with that in the control group, and the decrease in cognitive function significantly correlated with the MDA content. These findings suggest that long-term apple juice consumption decreases memory function, possibly through an increase in oxidative stress in the brain, in turn induced by fructose overloading. Fructose-induced cognitive dysfunction is likely mediated by mechanisms other than insulin resistance.

Effects of Non-Alcoholic Fatty Liver Disease on Visfatin and IL-6 Levels in Mice: An Immunohistochemical Study

Non-alcoholic Fatty Liver Disease (NAFLD) includes a wide range of diseases from simple fatty liver to steatohepatitis, fibrosis and cirrhosis. Alcoholic fatty liver disease and its more serious form, NAFLD, are related mostly to obesity and insulin resistance. Adipokines, secreted form fatty tissues, increases with weight gain and body-mass index (BMI). Previous studies showed that most adipokines increased with liver steatosis but changes of visfatin and IL-6 levels are still controversial. We applied a high dose fructose diet to mice via adding 30% w/v fructose to the drinking water for 4-6 weeks. High levels of liver damage and NAFLD were observed within the experiment group. Visfatin and IL-6 levels were also evaluated using immunohistochemistry. We found high levels of liver damage in fructose group along with increased levels of biochemical liver damage markers. Both IL-6 and visfatin staining were observed higher in the fructose group. Our study suggests that the IL-6 and visfatin levels were increased with obesity and liver damage. We aimed that this study will create an opportunity for new research with IL-6 and visfatin.

The effects of resveratrol on hepatic oxidative stress in metabolic syndrome model induced by high fructose diet.

The purpose of this study was to evaluate probable protective effects of resveratrol treatment on hepatic oxidative events in a rat model of metabolic syndrome (MetS). Thirty-two male adult rats were randomly divided into 4 groups: control, fructose, resveratrol, and fructose plus resveratrol. To induce MetS, fructose solution (20 % in drinking water) was used. Resveratrol (10 mg/kg/day) was given by oral gavage. All treatments were given for 8 weeks. Serum lipid profile, glucose and insulin levels, liver total oxidant status (TOS) levels and paraoxonase (PON), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were analyzed. Fructose-fed rats displayed statistically significant increases in TOS levels, and decreases in PON activity compared to the control group. Resveratrol treatment moderately prevented the decrease in liver PON activity caused by fructose. On the other hand, resveratrol, alone or in combination with fructose, did not change the TOS levels when compared to the fructose group. The SOD and CAT activities in all groups did not change. In this experimental design, high-fructose consumption led to elevated TOS levels and low PON activities. The resveratrol therapy shown beneficial effects on PON activity. However, it was found to behave like a prooxidant when administered together with fructose and alone in some parameters. Our results can inspire the development of new clinical therapy in patients with MetS (Tab. 2, Ref. 34).

Maternal dietary free or bound fructose diversely influence developmental programming of lipogenesis

BackgroundMaternal dietary choices throughout preconception, pregnancy, and lactation irreversibly affect the development of fetal tissues and organs, known as fetal programming. Recommendations tend to emphasize reducing added sugars. However, the impact of maternal dietary free or bound fructose in added sugars on developmental programming of lipogenesis is unknown.MethodsVirgin Sprague-Dawley rats were randomly divided into five groups. Rats were given feed and plain water (control) or water containing maltodextrin (vehicle), fructose, high-fructose corn syrup (HFCS) containing 55% fructose, sucrose (20% w/v) for 12 weeks before mating and throughout the pregnancy and lactation periods. Body weight, water, and feed intake were measured throughout the study. At the end of the lactation period, blood was drawn to determine the fasting levels of glucose, insulin, triglycerides, and non-esterified fatty acids (NEFA) in blood. Triglycerides and acetyl Co-A Carboxylase-1 (ACC1) levels in livers were analyzed, and insulin resistance was calculated.ResultsThe energy intake of dams in the HFCS group was higher than in the fructose group, while weight gain was less in the HFCS group than in the fructose group. HFCS resulted in greater insulin resistance in dams, whereas free fructose had a robust effect on the fetal programming of insulin resistance. Free fructose and HFCS in the maternal diet increased blood and liver triglycerides and NEFA content in pups. Furthermore, fructose and HFCS exposure increased phosphorylated ACC1 as compared to maltodextrin and control, indicating greater fatty acid synthesis in pups and dams.ConclusionDifferent types of added sugar in the maternal diet have different metabolic effects on the developmental programming of lipogenesis. Consequently, high fructose intake via processed foods may increase the risk for chronic diseases, and free fructose might contribute to developmental programming of chronic diseases more than bound fructose.

Assessment of fructose overload in the metabolic profile and oxidative/nitrosative stress in the kidney of senescent female rats

The aging process is a complex phenomenon that leads the body to several changes, affecting its integrity and resulting in chronic pathologies, which compromises health and quality of life of elderly people. Animals supplemented with fructose have been used as an experimental model for induction of insulin resistance. The objective of this study was to evaluate the metabolic effects and the levels of oxidative/nitrosative stress in the kidney of senescent rats with a high fructose intake. The animals were allocated into 4 groups: young control (Y), aged control (A), young fructose (YF) and aged fructose (AF). Groups Y and A received water and groups YF and AF received fructose (100g/L) in the water, both ad libitum. After 12weeks of high fructose intake, the animals were sacrificed to collect their kidneys, blood and the thoracic aorta. The results are presented as mean±SE, analyzed by the One-Way ANOVA test with Newman-Keuls post-test; significant at p<0.05. The fructose overload caused metabolic dysfunctions and insulin resistance, confirming the efficacy of the chosen model. In this study, we observed a body weight gain in the studied groups (except in the elderly fructose group), and an increase in general caloric intake, diuresis and adipose tissue; insulin resistance, increased fasting glucose, triglycerides and cholesterol in the fructose groups. We also found a loss of renal function, increased oxidative/nitrosative stress and inflammation, and a reduction of antioxidants and a lower vasodepressor response in the studied groups, especially those who consumed fructose. In summary, our data showed that aging or high fructose intake contributed to the increase of oxidative/nitrosative stress in animals, demonstrating that at the dose and the period of fructose treatment utilized in this study, fructose was not able to aggravate several aspects which were already altered by aging. We believe that the high fructose intake simulates most of the effects of aging, and this understanding would be useful to prevent or minimize many of the alterations caused by this condition.

Abstract P228: Chronically Enhanced Fructose Intake Induces Salt Sensitive Hypertension in Mice and Increases NKCC2 Phosphorylation

High fructose consumption is implicated in hypertension and renal damage in humans. The mechanisms for the renal effects of fructose are not clear. In normal rats, a high fructose diet (20%) does not increase blood pressure, but rapidly (one week) induces a salt sensitive increase in blood pressure. NaCl reabsorption by the thick ascending limb (TAL) is mediated by the NKCC2 cotransporter. Higher NKCC2 activity is involved in salt sensitive hypertension, and its phosphorylation is increased by fructose in rats. We hypothesized that high fructose (20% drinking water), would induce NKCC2 phosphorylation and induce salt sensitive hypertension in normal C57/Bl6J mice. To test this, mice were given 20% fructose in drinking water and after two weeks they were treated for 10 more weeks with either fructose alone or fructose plus 4% Na diet. Tail cuff systolic blood pressure (SBP) was measured after 3 weeks of training. Total NKCC2 expression, GAPDH and NKCC2 phosphorylation at Thre96/101 (P-NKCC2) were measured by Western blot in freshly isolated TALs. Baseline SBP was 112 ± 3 mmHg. A transient increase to 125± 4 mmHg ( p &lt;0.05) was observed after 1 week on fructose which later decreased to 119 ± 3 mmHg ( p =0.14) by week 2. At the end of week 2, high salt chow was added. BP remained normal for 3 weeks and then increased to 137 ± 11 mmHg ( p &lt;0.05) by week 4 on high salt, but not in fructose alone mice. After 10 weeks SBP remained elevated in the fructose plus high salt diet group (124 ± 3 vs 110 ± 5 mmHg; p &lt;0.05). Water intake and urine volume was similar between the two high fructose groups. After 10 weeks, fasting glucose was higher in all mice with fructose (fructose + HS: 231± 8, fructose: 218 ± 7, normal diet: 122 ± 4 mg/dL, p &lt;0.001). A fructose diet increased P-NKCC2 by 248 ± 82% (n=5, p &lt;0.01) by one week and by 61 ± 21% ( p &lt;0.05) at week 12. The combination of high-fructose high salt diet increased P-NKCC2 by 226 ± 75% ( p &lt;0.05) at 12 weeks. Transcriptome profiling of isolated mouse TALs showed that 20% fructose (7 days) increased the expression of genes upstream of the SPAK and AMPK pathway. We conclude that 20% fructose in drinking water leads to a salt dependent increase in SBP, which appears to occur after mice develop abnormalities in glucose metabolism.

Myocardial protective effect of L-carnitine in children with hand, foot and mouth disease caused by Coxsackie A16 virus

To investigate the myocardial protective effect of L-carnitine in children with hand, foot and mouth disease (HFMD) caused by Coxsackie A16 virus and possible mechanisms. A total of 60 HFMD children with abnormal myocardial enzyme after Coxsackie A16 virus infection were enrolled and randomly divided into L-carnitine group and fructose-1,6-diphosphate group (fructose group), with 30 children in each group. The two groups were given L-carnitine or fructose diphosphate in addition to antiviral and heat clearance treatment. Another 30 healthy children who underwent physical examination were enrolled as control group. The changes in myocardial zymogram, malondialdehyde (MDA), superoxide dismutase (SOD), and apoptosis factors sFas and sFasL after treatment were compared between groups. There was no significant difference in treatment response between the L-carnitine group and the fructose group (P>0.05). One child in the fructose group progressed to critical HFMD, which was not observed in the L-carnitine group. Before treatment, the L-carnitine group and the fructose group had significantly higher indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significantly lower level of SOD than the control group (P<0.05), while there were no significant differences in these indices between the L-carnitine group and the fructose group (P>0.05). After treatment, the L-carnitine group and the fructose group had significant reductions in the indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significant increase in the level of SOD (P<0.05); the fructose group had a significantly higher level of creatine kinase (CK) than the control group and the L-carnitine group, and there were no significant differences in other myocardial enzyme indices, MDA, sFas, and sFasL between the L-carnitine group and the fructose group, as well as between the L-carnitine and fructose groups and the control group (P>0.05). SOD level was negatively correlated with aspartate aminotransferase, lactate dehydrogenase (LDH), CK, and creatine kinase-MB (CK-MB) (r=-0.437, -0.364, -0.397, and -0.519 respectively; P<0.05), and MDA level was positively correlated with LDH and CK-MB (r=0.382 and 0.411 respectively; P<0.05). L-carnitine exerts a good myocardial protective effect in children with HFMD caused by Coxsackie A16 virus, possibly by clearing oxygen radicals and inhibiting cardiomyocyte apoptosis.

Fructose induced neurogenic hypertension mediated by overactivation of p38 MAPK to impair insulin signaling transduction caused central insulin resistance

Type 2 diabetes are at a high risk of complications related to hypertension, and reports have indicated that insulin levels may be associated with blood pressure (BP). Fructose intake has recently been reported to promote insulin resistance and superoxide formation. The aim of this study is to investigate whether fructose intake can enhance superoxide generation and impair insulin signaling in the NTS and subsequently elevate BP in rats with fructose-induced hypertension. Treatment with fructose for 4 weeks increased the BP, serum fasting insulin, glucose, homeostatic model assessment-insulin resistance, and triglyceride levels and reduced the serum direct high-density lipoprotein level in the fructose group. The Tempol treatment recovered the fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that fructose increased the p38- and fructose-induced phosphorylation of insulin receptor substrate 1 (IRS1S307) and suppressed AktS473 and neuronal nitric oxide synthase phosphorylation. Similarly, fructose was able to impair insulin sensitivity and increase insulin levels in the NTS. Fructose intake also increased the production of superoxide in the NTS. The results of this study suggest that fructose might induce central insulin resistance and elevate BP by enhancing superoxide production and activating p38 phosphorylation in the NTS.

Biofilm extracellular polysaccharides degradation during starvation and enamel demineralization.

This study was conducted to evaluate if extracellular polysaccharides (EPS) are used by Streptococcus mutans (Sm) biofilm during night starvation, contributing to enamel demineralization increasing occurred during daily sugar exposure. Sm biofilms were formed during 5 days on bovine enamel slabs of known surface hardness (SH). The biofilms were exposed to sucrose 10% or glucose + fructose 10.5% (carbohydrates that differ on EPS formation), 8x/day but were maintained in starvation during the night. Biofilm samples were harvested during two moments, on the end of the 4th day and in the morning of the 5th day, conditions of sugar abundance and starvation, respectively. The slabs were also collected to evaluate the percentage of surface hardness loss (%SHL). The biofilms were analyzed for EPS soluble and insoluble and intracellular polysaccharides (IPS), viable bacteria (CFU), biofilm architecture and biomass. pH, calcium and acid concentration were determined in the culture medium. The data were analyzed by two-way ANOVA followed by Tukey’s test or Student's t-test. The effect of the factor carbohydrate treatment for polysaccharide analysis was significant (p < 0.05) but not the harvest moment (p > 0.05). Larger amounts of soluble and insoluble EPS and IPS were formed in the sucrose group when compared to glucose + fructose group (p < 0.05), but they were not metabolized during starvation time (S-EPS, p = 0.93; I-EPS, p = 0.11; and IPS = 0.96). Greater enamel %SHL was also found for the sucrose group (p < 0.05) but the demineralization did not increase during starvation (p = 0.09). In conclusion, the findings suggest that EPS metabolization by S. mutans during night starvation do not contribute to increase enamel demineralization occurred during the daily abundance of sugar.

High-monosaccharide intake inhibits anorexigenic hypothalamic insulin response in male rats

Objective: The aim of this research is to evaluate if intake of 20% fructose solution is able to change the anorexigenic hypothalamic insulin action.Methods: Thirty day-old male Wistar rats were randomly assigned to one of the following groups: standard chow and water for the rats (Control group, C) and standard chow and 20% fructose solution for the rats (Fructose group, F).These treatments lasted 8 weeks. Three-month-old rats from group C and F received insulin or saline intracerebroventricular injections for evaluation of 24 h food intake, phosphorylated forms of the IR (p-IR) and Akt (p-Akt) proteins and quantified hypothalamic insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) proteins.Results: Insulin injection was able to decrease food intake in group C compared to 0.9% saline. However, insulin infusion failed to inhibit 24 h food intake in group F compared to 0.9% saline. The hypothalamic content of the IRS-1 was 37% higher in group F as well as p-Akt protein was significant higher vs. group C.Conclusion: We concluded that the 20% fructose solution compromised insulin signaling considering that it inhibited the anorexigenic hypothalamic response to acute injection of this hormone and increase of IRS-1 and p-Akt content.

Liver and Metformin: Lessons of a fructose diet in mice

Studies show that the continuous consumption of fructose can lead to nonalcoholic fatty liver disease (NAFLD) and steatohepatitis. We aimed to investigate the role of Metformin in an animal model of liver injury caused by fructose intake, focusing on the molecular markers of lipogenesis, beta-oxidation, and antioxidant defenses. Male three months old C57BL/6 mice were divided into control group (C) and fructose group (F, 47% fructose), maintained for ten weeks. After, the groups received Metformin or vehicle for a further eight weeks: control (C), control + Metformin (CM), fructose (F), and fructose + Metformin (FM). Fructose resulted in hepatic steatosis, insulin resistance and lower insulin sensitivity in association with higher mRNA levels of proteins linked with de novo lipogenesis and increased lipid peroxidation. Fructose diminished mRNA expression of antioxidant enzymes, and of proteins responsible for mitochondrial biogenesis. Metformin reduced de novo lipogenesis and increased the expression of proteins related to mitochondrial biogenesis, thereby increasing beta-oxidation and decreasing lipid peroxidation. Also, Metformin upregulated the expression and activity of antioxidant enzymes, providing a defense against increased reactive oxygen species generation. Therefore, a significant reduction in triglyceride accumulation in the liver, steatosis and lipid peroxidation was observed in the FM group. In conclusion, fructose increases de novo lipogenesis, reduces the antioxidant defenses, and diminishes mitochondrial biogenesis. After an extended period of fructose intake, Metformin treatment, even in continuing the fructose intake, can reverse, at least partially, the liver injury and prevents NAFLD progression to more severe states.