High fructose corn syrup ınduced liver and heart damage are not reversed with hazelnut consumption: In vivo study.

Effect of moderate intake of sweeteners on metabolic health in the rat

ABSTRACTLittle is known about the pathogenesis of high fructose corn syrup (HFCS) induced hepatic toxicity. We investigated hepatic lesions induced by chronic HFCS consumption and the protective effects of alpha-lipoic acid (ALA) on liver pathology. We used 24 rats allocated randomly into three groups of eight. The HFCS group was given in drinking water for 10 weeks. The ALA + HFCS group was given the same dose of HFCS and ALA also was administered during the last 6 weeks of the experiment. The control group was untreated. The rats were euthanized at the end of 10 weeks and 24 h after the last ALA administration. A significant increase was observed in the serum aspartate aminotransferase (AST) level of the HFCS group compared to controls. Tissue malondialdehyde (MDA) levels also increased significantly and catalase (CAT) activity decreased significantly in the HFCS group. Caspase-3 expression increased significantly in the HFCS group compared to controls. In the ALA treated group, the levels of MDA, CAT and caspase-3 returned to near control levels. HFCS caused hepatic toxicity by increasing oxidative stress and apoptosis. ALA administration ameliorated the pathological changes.

ABSTRACTThe objective of this study was to determine the effect of high fructose corn syrup (HFCS) and citric acid (CA) in broiler diets on performance, gut pH, immunity, antioxidant status and some blood parameters. A total of 120 Ross 308 chicks at the age of 0 days were divided into 4 groups with 3 subgroups of 10 chicks each: control (CON), 50 mg/kg HFCS, 30 mg/kg CA and 50 mg/kg HFCS + 30 mg/kg CA (HFCS + CA). It was determined that body weight gain (BWG) was highest in the CA group and was similar to the CON group, whereas it was lower in the HFCS + CA group than other groups (p < 0.05). The feed conversion rates of the CA and the CON groups were similar and lower than the others (p < 0.05). Carcass weights and ratios increased in the CA group (p < 0.05). There were significant differences between the weights of liver and pancreas of groups (p < 0.05). Serum high‐density lipoprotein (HDL)‐CHO and GLU levels increased in the HFCS + CA group (p < 0.05). Serum total cholesterol (TCHO) level in the HFCS group was similar to the CON group and lower than the other groups (p < 0.05). Serum tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) values were determined to be highest in the HFCS group and different from the CON group (p < 0.05). It was observed that HFCS negatively affected performance, whereas CA positively affected. HFCS + CA increased serum TCHO and HDL‐CHO levels and CA led to an increasing trend in total antioxidant status (TAS) level. Although HFCS had a positive effect on TNF‐α and IL‐1β, similar of immunoglobulin G (IgG) and immunoglobulin M (IgM) levels between groups was observed.

We investigated the harmful effects of high fructose corn syrup (HFCS) on learning and memory in the hippocampus and the ameliorative effects of melatonin (Mel). Thirty-six adult male Sprague Dawley rats were divided into three groups: Group I, control; Group II, HFCS; and Group III, HFCS+Mel. HFCS form F55 was prepared as a 20% fructose syrup solution. Rats in HFCS and HFCS+Mel groups were given drinking water for 10 weeks. Rats in the HFCS+Mel group have been given 10 mg/kg/day melatonin orally for the 6 weeks, in addition to HFCS 55. The Morris water maze (MWM) test was applied to all animals for 5 days to determine their learning and memory levels. After decapitation, one-half of the hippocampus samples were collected for western blot analysis, and another half of the tissues were collected for histopathological and immunohistochemical analyses. In the HFCS group, there was a significant difference between the time to find the platform in the MWM test and time spent in the quadrant between days 1 and 5 (P=0.037 and P=0.001, respectively). In addition, a decreased level of MT1A receptor, TNF-α, iNOS, osteopontin (OPN), and interleukin-6 (IL-6) expressions were significantly increased in the HFCS group. Melatonin treatment reversed MT1A receptor levels and TNF-α, iNOS, OPN, and IL-6 expressions. During the histopathological examination, increased neuronal degenerations were observed in the HFCS group. Melatonin ameliorated these changes. Consumption of HFCS caused deterioration of learning and memory in adult rats. We suggest that melatonin is effective against learning and memory disorders.

Global sugar consumption is at an all-time high. In previous studies, we and others have demonstrated that, compared with glucose (Gluc), consumption of fructose (Fruc) increases risk factors for cardiovascular disease (CVD), diabetes and metabolic syndrome. However, humans almost exclusively consume Fruc in combination with Gluc. Our aim was to study effects of Gluc, Fruc and their combination - high fructose corn syrup (HFCS) - and identify effects on metabolic risk factors. We performed a parallel-armed, double blinded intervention study wherein the subjects consumed beverages sweetened with 25% of their energy requirement (Ereq) as Gluc, Fruc or HFCS, or 17.5% Ereq as Fruc or HFCS, or Aspartame (ASP) for two weeks with their usual diet. Procedures, which included fasting and postprandial blood draws, were conducted over a 48-h period at baseline and at the end of intervention while subjects consumed standardized meals containing 30% Ereq as fat, 15% protein, 55% carbohydrate (mainly complex during baseline; complex + sweetened beverage during intervention). As expected, the increases for 24h triglyceride area under the curve (AUC), 24h uric acid AUC, and postprandial apoCIII were highest in both Fruc groups (all P&amp;lt;0.01 versus ASP), next highest in both HFCS groups (all P&amp;lt;0.05 25% Ereq HFCS versus ASP), and lowest in the Gluc group (all P&amp;gt;0.05 versus ASP). Unexpectedly, the increases of LDL- and non-HDL-cholesterol (C) and ApoB were highest in the HFCS groups (all P&amp;lt;0.001 25% HFCS versus ASP, P&amp;lt;0.01 versus Gluc). Re-analyzing the outcomes based on the amounts of Fruc and Gluc contained in the beverages revealed significant interactions between Fruc and Gluc on fasting and postprandial concentrations of LDL-C, non-HDL-C and ApoB (all P&amp;lt;0.01). While sole consumption of Fruc leads to increases of metabolic risk factors, those increases are exacerbated for several risk factors when Fruc is co-ingested with Gluc as HFCS. Disclosure B. Hieronimus: None. V. Medici: None. V. Lee: None. M. Nunez: None. P.J. Havel: Research Support; Self; Arrowhead Research, Bristol-Myers Squibb Company, Magnamosis Inc. K.L. Stanhope: None. Funding National Heart, Lung, and Blood Institute (1R01HL09133, 1R01HL107256); National Center for Research Resources (UL1RR024146); Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD051958); Office of Research on Women’s Health; Office of Dietary Supplements; National Institute on Aging (to K.L.S.)

Aims This study was designed to reveal the effect of probiotics and omega-3 fatty acids in a fatty liver model in rats induced by high-fructose corn syrup (HFCS). Methods In the study, 40 male Wistar Albino rats were used, and these rats were divided into five groups. HFCS was added to the drinking water (30% solution) of four groups (Groups 2, 3, 4, and 5) for three weeks, and the animals were fed ad libitum. At the end of three weeks, the rats in Groups 3, 4, and 5 were administered omega-3 fatty acids (400 mg/kg) and probiotics (1.5 × 109 cfu/mL/day) with the gavage method for four weeks. The body weights of rats were weighed and recorded before starting the experiment, at the end of the third week, and before the animals were sacrificed at the last week, all at the same hour. By subtracting the remaining amount of food and water from the daily food and water amount, the amount of food and water consumed was calculated. These values were recorded for seven weeks. At the end of the seven weeks, the rats were sacrificed after blood specimens and tissues were taken. Results Analyzing the changes in the food intake of each group within itself throughout the experiment, it was observed that there was an increase in the food intake in the control group; from the starting week to the last week, the food intake amount of the HFCS group began to decrease particularly after the second week; and it began to decrease after the third week in the groups that were administered probiotics and omega-3 fatty acids. The changes in the sacrifice weights in the HFCS + omega-3 fatty acid, HFCS + probiotic, and HFCS + probiotic + omega-3 fatty acid groups were found to be lower than that in the HFCS group. The maximum levels of glucose, ALT, ALP, serum cholesterol, triglyceride and AST were found to be in the HFCS group. It was determined that the minimum mean steatosis level was in the control group, while the maximum steatosis level was in the HFCS group. Conclusions As a result, there was a protective effect of probiotic and omega-3 fatty acid.

BackgroundAmerican maternal overnutrition negatively impacts fetal development. Several epidemiological and experimental studies have demonstrated that overconsumption of diets rich in fats and sugars can have effects spanning three generations. While the negative impact of high fructose corn syrup (HFCS), a component heavily present in many processed American foods, is well‐recognized, its effects during fetal development remain largely underexplored. Thus, this study aims to examine the placental and fetal hepatic effects of HFCS maternal overconsumption.MethodsAdult female Wistar rats were randomized in 2 experimental groups: HFCS Group received a 20% HFCS solution in drinking water for 30 days prior to and during pregnancy. Control Group received regular water. Prior to pregnancy, blood pressure was measured in both experimental groups by using tail‐cuff plethysmography. Fasting glucose readings were measured weekly. Terminal experiments were completed on day 21 of gestation. Placentas and fetal livers were isolated and further processed for analysis of Hypoxia‐Inducible Factor‐α (HIF‐α) expression, a classical transcription factor of hypoxia, using Western Blot. Blood samples were collected for biochemical analysis.ResultsPrior to pregnancy, HFCS group exhibited increased serum triglycerides (441.48 vs. 109.47 mg/dL), systolic (159.03 ± 12.04 vs. 136.29 ± 2.57 mmHg, p&lt;0.05) and diastolic blood pressures (114.66 ± 9.47 vs. 99.29 ± 2.49 mmHg, p&lt;0.05) compared to controls. No differences were found in glucose levels (98.17 ± 1.65 vs. 92.5 ± .24 mg/dL controls). At the terminal experimental protocol, HFCS group displayed increased HIF‐α expression in placenta (2.3 fold‐increase, p&lt;0.05) and fetal liver (3.1 fold increase, p&lt;0.001) compared to controls. Therefore, our results show hypoxic changes in both placental and fetal hepatic tissues. Moreover, oil red staining confirmed increased fat deposition in the maternal livers from HFCS group.ConclusionOur findings show that overconsumption of HFCS prior to and during pregnancy has a negative impact on offspring, as demonstrated by upregulation of hypoxic markers such as HIF‐α. We will further this study to determine whether other tissues undergo hypoxia and the mechanisms by which HFCS leads to hypoxia in maternal and fetal tissues.Support or Funding InformationIn‐house Grant NYITThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

This study investigated the ameliorative role of melatonin (MLT) and the effects of a long-term intake of high-fructose corn syrup (HFCS) on the male reproductive system. Thirty-six male Sprague Dawley rats were randomly divided into 3 groups as follows: Control, HFCS and HFCS+MLT. Testis and epididymal weights were measured. Malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, total testosterone levels, testicular histopathological damage scores were evaluated, and immunohistochemical analyses were performed on testicular tissue. Epididymal weights were significantly lower in the HFCS+MLT group than those of the control and HFCS groups. MDA was significantly increased, while SOD and CAT activities were reduced in the HFCS group compared with the control group. Administration of melatonin significantly increased SOD and CAT activities in the HFCS+MLT group. Histopathological evaluation revealed slight hyperaemia and oedema in the stromal tissue of rat testes in the HFCS group. Sperm count and Johnsen's testicular biopsy score (JTBS) were significantly decreased in the HFCS group. Immunohistochemical analysis revealed that HSP, iNOS, MDA, OPN and VEGF values were significantly increased in the HFCS group. However, melatonin ameliorated the immunohistochemical scoring. Our results showed that a long-term intake of HFCS caused testicular damage. Melatonin may be a promising pharmacological agent against testicular toxicity induced by HFCS.

Reduction of abdominal fat accumulation in rats by 8-week ingestion of a newly developed sweetener made from high fructose corn syrup

High fructose corn syrup (HFCS) has been shown to cause cardiovascular toxicity via oxidative stress and inflammation. The aim of this study is to demonstrate the protective effects of melatonin (MLT) against HFCS-induced endothelial and cardiac dysfunction via oxidative stress and inflammation. Thirty-two Sprague Dawley male rats were distributed into three groups as control, HFCS, and HFCS + MLT. HFCS form F55 was prepared as 20% fructose syrup solution and given to the rats through drinking water for 10 weeks, and MLT administrated 10 mg/kg/day orally for last 6 weeks in addition to F55. After decapitation, blood and half of the heart samples were collected for biochemical analysis and other half of the tissues for histopathological and immunohistochemical analysis. Aspartate transaminase, creatine kinase MB, lactate dehydrogenase, total oxidant status and oxidative stress index, and caspase-3 levels increased and total antioxidant status levels decreased significantly in HFCS group. MLT treatment reversed all these parameters. Histopathologically, hyperemia, endothelial cell damage and increased levels of angiogenin, C-reactive protein, inducible nitric oxide synthase, myeloperoxidase and decreased sirtuin-1 (SIRT-1) expressions were observed in HFCS group. MLT ameliorated all these changes. MLT has an anti-inflammatory, antioxidant, antiapoptotic effects on HFCS-induced cardiovascular toxicity through enhancing the expression of SIRT-1.

Alpha lipoic acid attenuates high-fructose-induced pancreatic toxicity.

With the growth of the food industry, fructose, the intake of which increases with food, causes obesity and metabolic syndrome. Kidney damage may develop from metabolic syndrome. Selenium (Se) participates in the structure of antioxidant enzymes and has a medicinal effect. In this work, the protective impact of Se on kidney damage produced by high-fructose corn syrup (HFCS) via endoplasmic reticulum (ER) stress was examined. The study comprised four groups, each consisting of ten experimental animals: control, HFCS (20%-HFCS), HFCS (20%-HFCS), + Se (0.3 mg/kg/day/po), and Se (0.3 mg/kg/day/po) alone. The duration of the experiment was 6 weeks. Kidney tissues were stained with hematoxylin and eosin for histological examination. Immunohistochemical analysis was conducted to assess TNF-α and caspase-3 levels. The spectrophotometric evaluation was performed to measure TOS (total oxidant status), TAS (total antioxidant status), and OSI (oxidative stress index) levels. The PERK, ATF4, CHOP, BCL-2, and caspase-9 gene expression levels were assessed by the RT-qPCR method. After Se treatment, histopathological abnormalities and TNF-α and caspase-3 levels in the HFCS+Se group decreased (p < 0.001). While TOS and OSI levels increased dramatically in the HFCS group, TAS values decreased significantly but improved after Se application (p < 0.001). The expression levels of the genes PERK, ATF4, CHOP, and caspase-9 were significantly lower in the HFCS group when compared to the HFCS+Se group (p < 0.05). Our findings suggest that Se may protect against ER stress, oxidative stress, apoptosis, and kidney damage caused by high-dose fructose consumption.

High-fructose corn syrup intake increases hepatic mitochondrial DNA copy number and methylation in adolescent rats

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.

Maternal high-fructose corn syrup consumption causes insulin resistance and hyperlipidemia in offspring via DNA methylation of the Pparα promoter region