Effects of High-Fructose Corn Syrup Addition to Broiler Diets on Performance, Carcass Yield, Visceral Weights, Gut pH and Some Blood Parameters.

BACKGROUND: This study hypothesizes that using different amounts of high-fructose corn syrup (HFCS) in broiler diets may improve performance. OBJECTIVES: This study aimed to determine the effects of HFCS added to broiler diets on performance, cecum pH and some biochemical parameters. METHODS: A total of 120 Ross 308 chicks at the age of 0 day were divided into three main groups with four subgroups each. The groups consisted of a control (CON), low-HFCS and high-HFCS groups. The CON group received a diet containing no HFCS, the low-HFCS diet contained 50 mg/kg HFCS, and the high-HFCS diet contained 100 mg/kg HFCS. Body weight gain, feed consumption, carcass weight, visceral weight and cecum pH values were examined as performance parameters. Blood samples were taken at the end of the experiment and used to spectrophotometrically determine triglyceride, total cholesterol, high-density lipoprotein (HDL-CHO), low-density lipoprotein (LDL-CHO), glucose (GLU), creatinine (CRE), uric acid and insulin concentrations, as well as aspartate aminotransferase and alanine aminotransferase activities and oxidative stress markers. Proinflammatory cytokine levels were measured using ELISA test kits. RESULTS: Feed consumption and body weight gain of the high-HFCS group decreased (p < 0.01). The feed conversion rate was negatively affected in both HFCS groups compared to the CON group (p < 0.01). The carcass yields of the groups linearly decreased with the increase of HFCS (p < 0.001). Serum LDL cholesterol (p < 0.05) and GLU (p < 0.01) levels were significantly lower in the HFCS groups than the CON. Serum CRE levels were higher in the low-HFCS group compared to the other groups (p < 0.001). The oxidative stress index (OSI) levels were lower in the low-HFCS group than the CON group (p < 0.05). CONCLUSION: The addition of 100 mg/kg HFCS to broiler diets negatively affected performance parameters, but HFCS supplementation positively affected biochemical parameters. In particular, low-HFCS supplementation decreased the OSI, indicating that it could possibly reduce oxidative stress. Accordingly, HFCS could be added to broiler diets at a level of 50 mg/kg.

Resistant starch reduces glycolysis by HK2 and suppresses high-fructose corn syrup-induced colon tumorigenesis.

BACKGROUND: The intake of high-fructose corn syrup (HFCS) may increase the risk of colorectal cancer (CRC). This study aimed to explore the potential effects and mechanisms of resistant starch (RS) in HFCS-induced colon tumorigenesis. METHODS: The azoxymethane/dextran sodium sulfate (AOM/DSS) and ApcMin/+ mice models were used to investigate the roles of HFCS and RS in CRC in vivo. An immunohistochemistry (IHC) staining analysis was used to detect the expression of proliferation-related proteins in tissues. 16S rRNA sequencing for microbial community, gas chromatography for short-chain fatty acids (SCFAs), and mass spectrometry analysis for glycolysis products in the intestines were performed. Furthermore, lactic acid assay kit was used to detect the glycolysis levels in vitro. RESULTS: RS suppressed HFCS-induced colon tumorigenesis through reshaping the microbial community. Mechanistically, the alteration of the microbial community after RS supplement increased the levels of intestinal SCFAs, especially butyrate, leading to the suppression of glycolysis and CRC cell proliferation by downregulating HK2. CONCLUSIONS: Our study identified RS as a candidate of protective factors in CRC and may provide a potential target for HFCS-related CRC treatment.

EFECTOS DE DIETAS RICAS EN FRUCTOSA AÑADIDA EN LA PATOGÉNESIS DEL HÍGADO GRASO NO ALCOHÓLICO / EFFECTS OF DIETS RICH IN ADDED FRUCTOSE ON THE PATHOGENESIS OF NON-ALCOHOLIC FATTY LIVER DISEASE

Introducción: El hígado graso no alcohólico se enmarca en un grupo de patologías de etiología multifactorial, en el que la alimentación tendría un papel protagónico. En este sentido, el consumo de dietas ricas en fructosa, en especial a partir de fructosa añadida o jarabe de maíz alto en fructosa, ha sido motivo de investigación por su probable rol en la patogénesis de esta enfermedad. Metodología: Se realizó una búsqueda de artículos en relación con los efectos de las dietas ricas en fructosa sobre parámetros que podrían afectar la esteatosis hepática con el objetivo de organizar las principales evidencias al respecto. Resultados: Los estudios analizados tienden a evidenciar asociaciones positivas entre estas dietas y un mayor riesgo de desarrollar disbiosis intestinal, pérdida de integridad de la barrera intestinal y esteatosis hepática. Conclusiones: Los antecedentes recopilados en la presente revisión muestran evidencia de que este tipo de dietas favorecerían una serie de eventos que pueden conducir al hígado graso no alcohólico; por lo tanto, procurar un consumo adecuado de este monosacárido representaría una interesante alternativa de prevención para esta patología

Introduction: The non-alcoholic fatty liver disease falls within the group of multifactorial etiology pathologies in which food would play an important role. It is in this regard that the consumption of diets rich in fructose, especially from added fructose or corn syrup in fructose, has been a subject of investigation due to its likely roll in the pathogenesis of this disease. Methodology: A research for articles was performed about the effects of very rich fructose diets on parameters who could affect the liver steatosis in order to organize the main evidences. Results: The studies analized tend to report positive association between this diets and a higher risk of intestinal dysbiosis, intestinal barrier loss and partially with increased hepatic steatosis. Conclusions: The records compiled in the present review show evidence that this type of diets promote a serie of events that could result in non-alcoholic fatty liver disease so try a adequate consumption of this monosaccharides it would represent an interesting alternative to prevent this pathology

Disproportionately higher cardiovascular disease risk and incidence with high fructose corn syrup sweetened beverage intake among black young adults-the CARDIA study.

BACKGROUND: The black/white heart disease mortality disparity began increasing in the early 1980's, coincident with the switch from sucrose to high-fructose-corn-syrup/(HFCS) in the US food supply. There has been more fructose in HFCS than generally-recognized-as-safe/GRAS, which has contributed to unprecedented excess-free-fructose/(unpaired-fructose) in foods/beverages. Average- per-capita excess-free-fructose, from HFCS, began exceeding dosages/(5-10 g) that trigger fructose-malabsorption in the early 1980's. Fructose malabsorption contributes to gut-dysbiosis and gut-in-situ-fructosylation of dietary peptides/incretins/(GLP-1/GIP) which forms atherosclerotic advanced-glycation-end-products. Both dysregulate gut endocrine function and are risk factors for cardiovascular disease/(CVD). Limited research shows that African Americans have higher fructose malabsorption prevalence than others. CVD risk begins early in life. METHODS: Coronary-Artery-Risk-Development-in-Adults/(CARDIA) study data beginning in 1985-86 with 2186 Black and 2277 White participants, aged 18-30 y, were used to test the hypothesis that HFCS sweetened beverage intake increases CVD risk/incidence, more among Black than White young adults, and at lower intakes; while orange juice-a low excess-free-fructose juice with comparable total sugars and total fructose, but a 1:1 fructose-to-glucose-ratio, i.e., low excess-free-fructose, does not. Cox proportional hazards models were used to calculate hazard ratios. RESULTS: HFCS sweetened beverage intake was associated with higher CVD risk (HR = 1.7) than smoking (HR = 1.6). CVD risk was higher at lower HFCS sweetened beverage intake among Black than White participants. Intake, as low as 3 times/wk, was associated with twice the CVD risk vs. less frequent/never, among Black participants only (HR 2.1, 95% CI 1.2-3.7; P = 0.013). Probability of an ordered relationship approached significance. Among Black participants, CVD incidence jumped 62% from 59.8/1000, among ≤ 2-times/wk, to 96.9/1000 among 3-6 times/wk consumers. Among White participants, CVD incidence increased from 37.6/1000, among ≤ 1.5-times/wk, to 41.1/1000, among 2 times/wk-once/d - a 9% increase. Hypertension was highest among Black daily HFCS sweetened beverage consumers. CONCLUSION: The ubiquitous presence of HFCS over-the-past-40 years, at higher fructose-to-glucose ratios than generally-recognized-as-safe, may have contributed to CVD racial disparities, due to higher fructose-malabsorption prevalence among Black individuals, unpaired/excess-free-fructose induced gut dysbiosis and gut fructosylation of dietary peptides/incretins (GLP-1/GIP). These disturbances contribute to atherosclerotic plaque; promote incretin insufficiency/dysregulation/altered satiety/dysglycemia; decrease protective microbiota metabolites; and increase hypertension, CVD morbidity and mortality.

Hepatic steatosis induced by nicotine plus Coca-Cola™ is prevented by nicotinamide riboside (NR).

Introduction: Cigarettes containing nicotine (Nic) are a risk factor for the development of cardiovascular and metabolic diseases. We reported that Nic delivered via injections or e-cigarette vapor led to hepatic steatosis in mice fed with a high-fat diet. High-fructose corn syrup (HFCS) is the main sweetener in sugar-sweetened beverages (SSBs) in the US. Increased consumption of SSBs with HFCS is associated with increased risks of non-alcoholic fatty liver disease (NAFLD). Nicotinamide riboside (NR) increases mitochondrial nicotinamide adenine dinucleotide (NAD+) and protects mice against hepatic steatosis. This study evaluated if Nic plus Coca-Cola™ (Coke) with HFCS can cause hepatic steatosis and that can be protected by NR. Methods: C57BL/6J mice received twice daily intraperitoneal (IP) injections of Nic or saline and were given Coke (HFCS), or Coke with sugar, and NR supplementation for 10 weeks. Results: Our results show that Nic+Coke caused increased caloric intake and induced hepatic steatosis, and the addition of NR prevented these changes. Western blot analysis showed lipogenesis markers were activated (increased cleavage of the sterol regulatory element-binding protein 1 [SREBP1c] and reduction of phospho-Acetyl-CoA Carboxylase [p-ACC]) in the Nic+Coke compared to the Sal+Water group. The hepatic detrimental effects of Nic+Coke were mediated by decreased NAD+ signaling, increased oxidative stress, and mitochondrial damage. NR reduced oxidative stress and prevented mitochondrial damage by restoring protein levels of Sirtuin1 (Sirt1) and peroxisome proliferator-activated receptor coactivator 1-alpha (PGC1) signaling. Conclusion: We conclude that Nic+Coke has an additive effect on producing hepatic steatosis, and NR is protective. This study suggests concern for the development of NAFLD in subjects who consume nicotine and drink SSBs with HFCS.

Effects of Excessive High-fructose Corn Syrup Drink Intake in Middle-aged Mice.

BACKGROUND/AIM: The global prevalence of type 2 diabetes (T2D) continues to increase, necessitating the need for understanding the causes of its development. The widespread use of high-fructose corn syrup (HFCS) in drinks and diets is suspected to play a role in metabolic disorders. Although many studies have reported on the effects of excessive HFCS and excessive energy intakes in middle-aged individuals, few have focused on energy restriction. This study aimed to investigate the effects of excessive HFCS drink intake under energy restriction on developing T2D in early middle-aged mice. MATERIALS AND METHODS: Early middle-aged mice were divided in HFCS and control groups; they were provided either 10% HFCS water or deionized water ad libitum for 12 weeks, respectively. Total energy intake was controlled using a standard rodent diet. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), tissue weight measurements, serum parameter analyses, and mRNA expression assessments were performed. RESULTS: No increase in body and adipose tissue weight was observed with excessive HFCS intake under energy restriction. Moreover, serum lipid parameters did not differ from those of controls. However, in the OGTT and ITT, the HFCS group showed higher blood glucose levels than the control group. Moreover, the pancreatic weight and insulin II mRNA expression were reduced. CONCLUSION: The excessive HFCS drink intake under energy restriction did not induce obesity; however, it induced impaired glucose tolerance, indicating its negative effects on the pancreas in early middle-aged mice. When translated in human physiology, our results show that even if one does not become obese, excessive HFCS may affect the overall metabolic mechanism; these effects may vary depending on age.

Development of a tamarind-based functional beverage with partially-hydrolyzed agave syrup and the health effects of its consumption in C57BL/6 mice.

Excess consumption of sweetened beverages is associated with a global rise in metabolic diseases. Tamarind and partially-hydrolyzed agave syrup have potential for developing healthier beverages. Our objective was to develop a functional beverage using these ingredients (PH-AS-B). We also evaluate shelf-life stability (physicochemical, microbiological, and antioxidant properties) and health effects in C57BL/6 mice compared with tamarind beverages sweetened with glucose or fructose. Optimal tamarind extraction conditions were a 1:10 ratio (g pulp/mL water) and boiling for 30 min, and the resulting beverage had a shelf life of two months at 4 °C. Non-volatile metabolites were identified using HPLC/MS. PH-AS-B was associated with decreased blood cholesterol (5%) and triglyceride (20-35%) concentrations in healthy mice as well as lower lipid (82%) concentrations and evidence of protein oxidation (42%) in the liver, compared with glucose- and fructose-sweetened tamarind beverages. In conclusion, PH-AS-B was stable and associated with beneficial metabolic properties in healthy mice.

The Impact of the High-Fructose Corn Syrup on Cardiac Damage via SIRT1/PGC1-α Pathway: Potential Ameliorative Effect of Selenium.

High-fructose corn syrup (HFCS) has been a subject of intense debate due to its association with cardiovascular risks. This study investigates the potential protective effects of selenium (Se) supplementation against cardiac damage induced by HFCS. Thirty-two male Wistar albino rats were divided into four equal groups: control, CS (20%-HFCS), CS with Se (20%-HFCS, 0.3 mg/kg-Se), and Se (0.3 mg/kg-Se) only. After a 6-week period, heart and aorta tissues were collected for histopathological, immunohistochemical, biochemical, and genetic analyses. HFCS consumption led to severe cardiac pathologies, increased oxidative stress, and altered gene expressions associated with inflammation, apoptosis, and antioxidant defenses. In the CS group, pronounced oxidative stress within the cardiac tissue was concomitant with elevated Bcl-2-associated X protein (Bax) expression and diminished expressions of B-cell-lymphoma-2 (Bcl-2), nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), and silenced information regulator 1 (SIRT1). Se supplementation mitigated these effects, showing protective properties. Immunohistochemical analysis supported these findings, demonstrating decreased expressions of caspase-3, tumor necrosis factor-alpha (TNF-α), IL-1ß, and vascular endothelial growth factor (VEGF) in the CS + Se group compared to the CS group. The study suggests that Se supplementation exerts anti-inflammatory, antioxidant, and antiapoptotic effects, potentially attenuating HFCS-induced cardiovascular toxicity. These findings highlight the importance of dietary considerations and selenium supplementation in mitigating cardiovascular risks associated with HFCS consumption.

40 years of adding more fructose to high fructose corn syrup than is safe, through the lens of malabsorption and altered gut health-gateways to chronic disease.

Labels do not disclose the excess-free-fructose/unpaired-fructose content in foods/beverages. Objective was to estimate excess-free-fructose intake using USDA loss-adjusted-food-availability (LAFA) data (1970-2019) for high fructose corn syrup (HFCS) and apple juice, major sources of excess-free-fructose, for comparison with malabsorption dosages (~ 5 g-children/ ~ 10 g-adults). Unlike sucrose and equimolar fructose/glucose, unpaired-fructose triggers fructose malabsorption and its health consequences. Daily intakes were calculated for HFCS that is generally-recognized-as-safe/ (55% fructose/45% glucose), and variants (65/35, 60/40) with higher fructose-to-glucose ratios (1.9:1, 1.5:1), as measured by independent laboratories. Estimations include consumer-level-loss (CLL) allowances used before (20%), and after, subjective, retroactively-applied increases (34%), as recommended by corn-refiners (~ 2012). No contributions from crystalline-fructose or agave syrup were included due to lack of LAFA data. High-excess-free-fructose-fruits (apples/pears/watermelons/mangoes) were not included. Eaten in moderation they are less likely to trigger malabsorption. Another objective was to identify potential parallel trends between excess-free-fructose intake and the "unexplained" US asthma epidemic. The fructose/gut-dysbiosis/lung axis is well documented, case-study evidence and epidemiological research link HFCS/apple juice intake with asthma, and unlike gut-dysbiosis/gut-fructosylation, childhood asthma prevalence data spans > 40 years. Results Excess-free-fructose daily intake for individuals consuming HFCS with an average 1.5:1 fructose-to-glucose ratio, ranged from 0.10 g/d in 1970, to 11.3 g/d in 1999, to 6.5 g/d in 2019, and for those consuming HFCS with an average 1.9:1 ratio, intakes ranged from 0.13 g/d to 16.9 g/d (1999), to 9.7 g/d in 2019, based upon estimates with a 20% CLL allowance. Intake exceeded dosages that trigger malabsorption (~ 5 g) around ~ 1980. By the early 1980's, tripled apple juice intake had added ~ 0.5 g to average-per-capita excess-free-fructose intake. Contributions were higher (~ 3.8 g /4-oz.) for individuals consuming apple juice consistent with a healthy eating pattern (4-oz. children, 8-oz. adults). The "unexplained" childhood asthma epidemic (1980-present) parallels increasing average-per-capita HFCS/apple juice intake trends and reflects epidemiological research findings. Conclusion Displacement of sucrose with HFCS, its ubiquitous presence in the US food-supply, the industry practice of adding more fructose to HFCS than generally-recognized-as-safe, and increased use of apple juice/crystalline fructose/agave syrup in foods/beverages has contributed to unprecedented excess-free-fructose intake levels, fructose malabsorption, gut-dysbiosis and gut-fructosylation (immunogen burden)-gateways to chronic disease.

Safety assessment of high fructose corn syrup and fructose used as sweeteners in foods.

High Fructose Corn Syrup (HFCS) and Fructose (FR) are widely used sweeteners in many foods and beverages. This study aimed at investigating the cytotoxic effects of HFCS (5%-30%) and FR (62.5-2000 µg/mL) using MTT assay in Human Hepatocellular Carcinoma (HepG2) cells, and genotoxic effects of using Chromosome Aberrations (CAs), Sister Chromatid Exchanges (SCEs), Micronuclei (MN) and comet assays in human lymphocytes. HFCS significantly reduced the cell viability in HepG2 cells at between 7.5% and 30% for 24 and 48 h. 30% HFCS caused a very significant toxic effect. FR had a cytotoxic effect in HepG2 cells at all treatments. However, as fructose concentration decreased, the cell viability decreased. HFCS (10%-20%) and FR (250-2000 µg/mL) decreased the mitotic index at higher concentrations. IC50 value was found to be a 15% for 48 h. IC50 value of FR was detected as 62.5 µg/mL for 24 h and 48 h. HFCS significantly increased CAs frequency at 15% and 20%. FR significantly increased the frequency of CAs at 250, 1000, and 2000 µg/mL for 48 h. Both sweeteners increased the frequency of SCEs at all concentrations. HFCS (15% and 20%) and FR (250, 1000, and 2000 µg/mL) induced MN frequency at higher concentrations. HFCS caused DNA damage in comet assay at 10% -30%. FR increased tail intensity and moment at 125-2000 µg/mL and tail length at 62.5, 250 and 500 µg/mL. Therefore, HFCS and FR are clearly seen to be cytotoxic and genotoxic, especially at higher concentrations.

HFCS and FR exhibited cytotoxic effect at HepG2 and human lymphocytes at higher concentrations.Both sweeteners increased the frequencies of CAs and SCEs at higher concentrations.HFCS caused DNA damage at 10% -30% concentrations.HFCS (15% and 20%) and FR (250, 1000, and 2000 µg/mL) induced MN frequency.

Construction and investigation of multi-enzyme immobilized matrix for the production of HFCS.

Enzymes are biological molecules that act as catalysts and speed up the biochemical reactions. The world's biotechnological ventures are development of enzyme productiveness, and advancement of novel techniques for thriving their shelf existence. Nowadays, the most burning questions in enzyme technology are how to improve the enzyme productivity and reuse them. The immobilization of enzymes provides an excellent scope to reuse the enzymes several times to increase productivity. The main aim of the present study is the establishment of an immobilized multi-enzyme bio-system engineering process for the production of High-fructose corn syrup (HFCS) with an industrial focus. In this study, multi-enzyme such as α-amylase, glucoamylase and glucose isomerase were immobilized in various support matrices like sodium alginate, sawdust, sugarcane bagasse, rice bran and combination of alginate with cellulosic materials. The activities of the immobilized multi-enzyme system for the production of HFCS from the starch solution were determined. The multi-enzyme immobilized in sodium alginate shows better fructose conversion than free enzyme. Among the support matrices, multi-enzyme immobilized in sawdust produced total 80.74 mg/mL of fructose from starch solution and it was able to be used in several production cycles. On the other hand, multi-enzyme immobilized in combination of sodium alginate and sawdust produced the maximum amount of fructose (total 84.82 mg/mL). The free enzyme produced 17.25 mg/mL of fructose from the starch solution in only a single cycle. In this study a new fixed bed immobilized multi-enzyme bioreactor system was developed for the production of HFCS directly from starch. This finding will create a new opportunity for the application of immobilized multi-enzyme systems in many sectors of industrial biotechnology.

Effects of Consuming Beverages Sweetened with Fructose, Glucose, High-Fructose Corn Syrup, Sucrose, or Aspartame on OGTT-Derived Indices of Insulin Sensitivity in Young Adults.

(1) Background: Clinical results on the effects of excess sugar consumption on insulin sensitivity are conflicting, possibly due to differences in sugar type and the insulin sensitivity index (ISI) assessed. Therefore, we compared the effects of consuming four different sugars on insulin sensitivity indices derived from oral glucose tolerance tests (OGTT). (2) Methods: Young adults consumed fructose-, glucose-, high-fructose corn syrup (HFCS)-, sucrose-, or aspartame-sweetened beverages (SB) for 2 weeks. Participants underwent OGTT before and at the end of the intervention. Fasting glucose and insulin, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), glucose and insulin area under the curve, Surrogate Hepatic Insulin Resistance Index, Matsuda ISI, Predicted M ISI, and Stumvoll Index were assessed. Outcomes were analyzed to determine: (1) effects of the five SB; (2) effects of the proportions of fructose and glucose in all SB. (3) Results: Fructose-SB and the fructose component in mixed sugars negatively affected outcomes that assess hepatic insulin sensitivity, while glucose did not. The effects of glucose-SB and the glucose component in mixed sugar on muscle insulin sensitivity were more negative than those of fructose. (4) Conclusion: the effects of consuming sugar-SB on insulin sensitivity varied depending on type of sugar and ISI index because outcomes assessing hepatic insulin sensitivity were negatively affected by fructose, and outcomes assessing muscle insulin sensitivity were more negatively affected by glucose.

Impact of maternal fructose intake on liver stem/progenitor cells in offspring: Insights into developmental origins of health and disease.

AIMS: The developmental origin of health and disease (DOHaD) theory postulates that poor nutrition during fetal life increases the risk of disease later in life. Excessive fructose intake has been associated with obesity, diabetes, and nonalcoholic fatty liver disease, and maternal fructose intake during pregnancy has been shown to affect offspring health. In this study, we investigated the effects of high maternal fructose intake on the liver stem/progenitor cells of offspring. MAIN METHOD: A fructose-based DOHaD model was established using Sprague-Dawley rats. Small hepatocytes (SHs), which play an important role in liver development and regeneration, were isolated from the offspring of dams that were fed a high-fructose corn syrup (HFCS) diet. The gene expression and DNA methylation patterns were analyzed on postnatal day (PD) 21 and 60. KEY FINDINGS: Maternal HFCS intake did not affect body weight or caloric intake, but differences in gene expression and DNA methylation patterns were observed in the SHs of offspring. Functional analysis revealed an association between metabolic processes and ion transport. SIGNIFICANCE: These results suggest that maternal fructose intake affects DNA methylation and gene expression in the liver stem/progenitor cells of offspring. Furthermore, the prolonged retention of these changes in gene expression and DNA methylation in adulthood (PD 60) suggests that maternal fructose intake may exert lifelong effects. These findings provide insights into the DOHaD for liver-related disorders and highlight the importance of maternal nutrition for the health of the next generation.

Protective effect of vitamin D on learning and memory impairment in rats induced by high fructose corn syrup.

In our study, we aimed to investigate the negative effects of the prefrontal cortex (PFC)-associated impairment of cholinergic activity on memory and learning caused by high fructose corn syrup (HFCS) and the protective role of vitamin D in adolescent rats. Twenty-four animals were divided into three groups as control, HFCS group (11 % HFCS-55 solution, ad libitum) and HFCS+ Vit D (42 µg/kg/day). Elevated Plus Maze (EPM), Forced Swim Test (FST), and Morris Water Maze (MWM, performed from day 23) tests were applied to all animals. Fluid intake consumption of the rats was measured daily, weight gain and blood glucose were measured weekly. After 31 days of treatment, the rats were sacrificed and PFC tissue was removed for biochemical, histopathological and immunohistochemical analyses. In HFCS group, fluid consumption, blood glucose, malondialdehyde (MDA) levels, degenerative neuron count and choline acetyltransferase (ChAT) expression were significantly increased; superoxide dismutase (SOD), catalase (CAT) enzyme activity and brain-derived neurotrophic factor (BDNF) expression were significantly decreased. In addition, the time spent in the enclosed arm in EPM was increased, the immobility time in FST was, and the time spent in the target quadrant in MWM was significantly decreased. Vitamin D treatment reversed all these parameters. In conclusion, HFCS caused an increase in the number of degenerative neurons in the PFC, disrupted cholinergic activity and negatively affected learning-memory functions. Vitamin D, decreased the number of degenerative neurons, increased cholinergic activity and positively affected learning and memory performance. BRIEF SYNOPSIS: In this study, prefrontal cortex damage was investigated in adolescent rats fed high fructose corn syrup. The effect of vitamin D on prefrontal cortex damage was evaluated.

Bioactive dipeptides mitigate high-fat and high-fructose corn syrup diet-induced metabolic-associated fatty liver disease via upregulation of Nrf2/HO-1 expressions in C57BL/6J mice.

Metabolic-associated fatty liver disease (MAFLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), is a common liver disease characterized by an abnormal buildup of fat in liver. This study aimed to investigate whether bioactive dipeptides mitigate high-fat and high-fructose corn syrup diet (HFFD)-induced MAFLD in C57BL/6J mice. Sixty male C57BL/6J mice were randomly divided into six groups. The naïve group (untreated) was fed a standard chow diet and other groups were fed with HFFD along with vehicle and bioactive dipeptides treatment throughout experiment period. The control group received vehicle, YF10 and YF50 groups received Tyr-Phe, 10 and 50 mg/kg/day, FY10 and FY50 groups received Phe-Tyr, 10 and 50 mg/kg/day. At the end of experiment, body weight was recorded, and glucose homeostasis was assessed. Mice were sacrificed and blood samples were collected to measure biochemical parameters. Further, liver, visceral fat pads, and other organs were acutely dissected, weighed, and processed. Histopathological and immunohistochemical changes were analyzed. Long-term HFFD feeding resulted in elevated body weight gain, liver weight, visceral adiposity, liver injury, fasting hyperglycemia, hyperinsulinemia, and hyperlipidemia. It also increased severe hepatic steatosis, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and lipid peroxidation. However, bioactive dipeptides dose-dependently alleviated these complications which are associated with MAFLD by modulating adipokines secretion and antioxidant defense system via upregulation of Nrf2/HO-1 expressions. This study highlights potential of bioactive dipeptides as a promising approach for prevention and/or treatment of MAFLD induced by HFFD, providing novel insights into alternative therapeutic strategies.

Interaction between Prenatal and Postnatal Exposure to High-Fructose Corn Syrup Increases Gene Expression of Tnfa in Hippocampus of Offspring.

Concerns about the negative intergenerational effects of excessive fructose intake are being raised, with evidence suggesting that prenatal fructose intake increases susceptibility to metabolic and cognitive dysfunction later in life. In the present study, we hypothesized that prenatal and postnatal fructose intake acts synergistically to impact on hippocampus of adult offspring. Female Sprague-Dawley rats received distilled water or 20% high-fructose corn syrup (HFCS) solution in addition to standard chow throughout gestation and lactation. Male offspring were weaned at postnatal day 21 (PD21) and were randomized to receive distilled water or 20% HFCS solution until PD60. The following experimental groups were: CC: distilled water dams and post-weaning distilled water, CH: distilled water dams and post-weaning HFCS solution, HC: HFCS solution dams and post-weaning distilled water and HH: HFCS solution dams and post-weaning HFCS solution. The synergistic effect of maternal and post-weaning HFCS intake on the hippocampus was investigated by studying the expression of pro-inflammatory cytokine genes (Tnfa, Il1b, and Il6). At weaning, expression levels of pro-inflammatory cytokines between the offspring of the distilled water and HFCS solution fed dams were not significantly different. At PD60, Tnfa expression was significantly higher in the HH group than in the CC, HC and CH groups, whereas no significant differences were found between the CC, HC, and CH groups. These results suggest that postnatal fructose intake negatively impacts the hippocampus by acting synergistically with prenatal fructose intake.

Maternal High-Fructose Corn Syrup Intake Impairs Corticosterone Clearance by Reducing Renal 11ß-Hsd2 Activity via miR-27a-Mediated Mechanism in Rat Offspring.

We previously reported that maternal fructose consumption increases blood corticosterone levels in rat offspring. However, the underlying mechanism of action remains unclear. In the present study, we aimed to elucidate the molecular mechanism by which maternal high-fructose corn syrup (HFCS) intake increases circulating GC levels in rat offspring (GC; corticosterone in rodents and cortisol in humans). Female Sprague Dawley rats received HFCS solution during gestation and lactation. The male offspring were fed distilled water from weaning to 60 days of age. We investigated the activities of GC-metabolizing enzymes (11ß-Hsd1 and 11ß-Hsd2) in various tissues (i.e., liver, kidney, adrenal glands, muscle, and white adipose tissue) and epigenetic modification. 11ß-Hsd2 activity decreased in the kidney of the HFCS-fed dams. Moreover, the epigenetic analysis suggested that miR-27a reduced Hsd11b2 mRNA expression in the kidney of offspring. Maternal HFCS-induced elevation of circulating GC levels in offspring may be explained by a decrease in 11ß-Hsd2 activity via renal miR-27a expression. The present study may allow us to determine one of the mechanisms of GC elevation in rat offspring that is often observed in the developmental origins of the health and disease (DOHaD) phenomenon.

Non-Nutritive Sweetened Beverages Impair Therapeutic Benefits of Metformin in Prediabetic Diet-Induced Obese Mice.

Metformin, a frontline therapy for type 2 diabetes and related metabolic diseases, results in variable outcomes. This study aimed to investigate whether sweetened beverages (caloric or non-caloric) affect the therapeutic benefits of metformin on glucose, food intake, and weight loss in diet-induced obesity. Mice were given a high-fat diet and sweetened water for 8 weeks to induce obesity and glucose intolerance. Then, mice were randomized to receive metformin in either water, high-fructose corn syrup (HFCS), or the non-nutritive sweetener saccharin for 6 weeks. After 6 weeks of metformin treatment, all groups had improved glucose tolerance compared to pretreatment. However, saccharin resulted in worse glucose tolerance and weight gain outcomes than the water or HFCS groups and correlated with lower plasma growth differentiation factor 15 levels. In conclusion, reducing non-nutritive sweetener consumption during metformin therapy is recommended to avoid impairing the therapeutic effects of metformin on body weight and glucose homeostasis.

TRPM2 may be involved in high fructose corn syrup-induced anxiety-like behavior in adult male rats.

Excessive high fructose corn syrup (HFCS) consumption is known to cause oxidative stress, which induces transient receptor potential melastatin type 2 (TRPM2) channel gating. Oxidative stress-induced TRPM2 gating is suggested to play an important role in neurons, indicating a role for the TRPM2 channel in a variety of neuropsychiatric disorders including depression and anxiety. We investigated the effects of HFCS and chronic immobilization stress (CIS) on TRPM2 channel immunoreactivity, anxiety, and depressive-like behaviors in adult male rats. The male rats (n=8/group) were divided into 4 groups: Control, 20% HFCS (F20), 40% HFCS (F40), and stress. The control group received tap water, and F20 and F40 groups were exposed to HFCS 20% and 40% respectively for 14 consecutive days. Rats in the stress group were subjected to immobilization stress for 3 or 6 hours daily in the first and second weeks to induce CIS. Then, light/dark tests, open field tests (OFT), and tail suspension tests (TST) were performed, respectively. In the light/dark test, the time spent in the dark chamber significantly increased in all groups vs the control group (P<0.01). In support of this result, time spent in the light chamber significantly decreased in all groups vs the control group (P<0.01). Besides, CIS significantly increased depressive-like behavior in the stress group vs the control group (P<0.05). In serum hormone levels, corticosterone (CORT) levels significantly increased in the F40 and stress groups vs the control group (P<0.01). TRPM2 immunoreactivity significantly increased in the hippocampus, prefrontal cortex (PFC), nucleus accumbens (NaC), and amygdala regions by HFCS and CIS treatments. For the first time in the present study,  showed that f increased immunoreactivity of the TRPM2 cation channels may be linked to the anxiety-like behavior induced by HFCS.

High Fructose Corn Syrup Accelerates Kidney Disease and Mortality in Obese Mice with Metabolic Syndrome.

The presence of obesity and metabolic syndrome is strongly linked with chronic kidney disease (CKD), but the mechanisms responsible for the association are poorly understood. Here, we tested the hypothesis that mice with obesity and metabolic syndrome might have increased susceptibility to CKD from liquid high fructose corn syrup (HFCS) by favoring the absorption and utilization of fructose. We evaluated the pound mouse model of metabolic syndrome to determine if it showed baseline differences in fructose transport and metabolism and whether it was more susceptible to chronic kidney disease when administered HFCS. Pound mice have increased expression of fructose transporter (Glut5) and fructokinase (the limiting enzyme driving fructose metabolism) associated with enhanced fructose absorption. Pound mice receiving HFCS rapidly develop CKD with increased mortality rates associated with intrarenal mitochondria loss and oxidative stress. In pound mice lacking fructokinase, the effect of HFCS to cause CKD and early mortality was aborted, associated with reductions in oxidative stress and fewer mitochondria loss. Obesity and metabolic syndrome show increased susceptibility to fructose-containing sugars and increased risk for CKD and mortality. Lowering added sugar intake may be beneficial in reducing the risk for CKD in subjects with metabolic syndrome.