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High-Fructose Corn Syrup Promotes Proinflammatory Macrophage Activation via ROS-Mediated NF-κB Signaling and Exacerbates Colitis in Mice

ABSTRACT: we focused on HFCS and found that HFCS aggravates colitis by altering the intestinal immune microenvironment. Our data demonstrate that short-term consumption of HFCS upregulates the proportion of macrophages in IBD mice but not in healthy mice. HFCS promotes proinflammatory cytokine production through reactive oxygen species (ROS)-mediated nuclear factor-κB (NF-κB) signaling. Our work unveils the important role of macrophages in HFCS-induced exacerbation of colitis and reveals the mechanism of how HFCS immunologically aggravates IBD.

ORGANISM(S): Mus musculus

PROVIDER: GSE186953 | GEO | 2024/10/01

REPOSITORIES: GEO

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High-Fructose Corn Syrup Promotes Proinflammatory Macrophage Activation via ROS-Mediated NF-κB Signaling and Exacerbates Colitis in Mice

Project description:High-Fructose Corn Syrup Promotes Proinflammatory Macrophage Activation via ROS-Mediated NF-κB Signaling and Exacerbates Colitis in Mice

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The Role of Fructose, Sucrose and High-fructose Corn Syrup in Diabetes.

Project description:Concerns are growing regarding the role of dietary sugars in the development of obesity and cardiometabolic diseases, including diabetes. High-fructose corn syrup (HFCS) and sucrose are the most important dietary sweeteners. Both HFCS and sucrose have overlapping metabolic actions with adverse effects attributed to their fructose moiety. Ecological studies have linked the rise in fructose availability with the increases in obesity and diabetes worldwide. This link has been largely underpinned by animal models and select human trials of fructose overfeeding at high levels of exposure. Although prospective cohort studies have shown significant associations comparing the highest with the lowest levels of intake sugar-sweetened beverages, these associations are small, do not hold at moderate levels of intake and are subject to collinearity effects from related dietary and lifestyle factors. Most systematic reviews and meta-analyses from controlled feeding trials have shown that fructose-containing sugars in isocaloric exchange for other carbohydrates do not show evidence of harm and, in the case of fructose, may even have advantages for glycaemic control, especially at small doses. Nevertheless, trials in which fructose-containing sugars supplement diets with excess energy have shown adverse effects, effects that appear more attributable to the excess energy than the sugar. There is no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects, although there is potentially cause for concern where fructose is provided at high doses or contributes excess energy to diets. Further investigation is warranted due to the significant knowledge gaps and weaknesses in existing research.

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High-fructose corn syrup enhances intestinal tumor growth in mice.

Project description:Excessive consumption of beverages sweetened with high-fructose corn syrup (HFCS) is associated with obesity and with an increased risk of colorectal cancer. Whether HFCS contributes directly to tumorigenesis is unclear. We investigated the effects of daily oral administration of HFCS in adenomatous polyposis coli (APC) mutant mice, which are predisposed to develop intestinal tumors. The HFCS-treated mice showed a substantial increase in tumor size and tumor grade in the absence of obesity and metabolic syndrome. HFCS increased the concentrations of fructose and glucose in the intestinal lumen and serum, respectively, and the tumors transported both sugars. Within the tumors, fructose was converted to fructose-1-phosphate, leading to activation of glycolysis and increased synthesis of fatty acids that support tumor growth. These mouse studies support the hypothesis that the combination of dietary glucose and fructose, even at a moderate dose, can enhance tumorigenesis.

| S-EPMC6487857 | biostudies-literature

High-Fructose Corn Syrup Enhances Intestinal Tumor Growth in Mice

Project description:Excessive consumption of beverages sweetened with high-fructose corn syrup (HFCS) is associated with obesity and with an increased risk of colorectal cancer. Whether HFCS contributes directly to tumorigenesis is unclear. We investigated the effects of daily oral administration of HFCS in APC mutant mice, which are predisposed to develop intestinal tumors. The HFCS-treated mice showed a dramatic increase in tumor size and tumor grade in the absence of obesity or metabolic syndrome. HFCS increased the levels of fructose and glucose in the intestinal lumen and serum, respectively, and the tumors absorbed both sugars. Within the tumors, fructose was converted to fructose-1-phosphate, leading to activation of glycolysis and increased synthesis of fatty acids that support tumor growth. These mouse studies support the hypothesis that the combination of dietary glucose and fructose, even at a moderate dose, can enhance tumorigenesis.

2019-03-29 | GSE126858 | GEO

Alcohol promotes macrophage M2b polarization in colitis by modulating the TRPV1-MAPK/NF-kB pathways

Project description:Macrophages are key immune cells in inflammatory bowel disease (IBD) that can exhibit different phenotypes and promote inflammation. Alcohol consumption is associated with increased risk and severity of IBD. We performed in vitro and in vivo experiments with dextran sodium sulfate-induced mice colitis model, peritoneal macrophages and RAW264.7 cell line to investigate the effect and mechanism of alcohol on macrophages in colitis. Our study has found that alcohol exacerbates colitis in mice, increases the aggregation of colonic macrophages, and promotes the production of various inflammatory factors. Alcohol increases lipopolysaccharides (LPS)-induced calcium influx in macrophages, which is inhibited by the TRPV1 antagonist Capsazepine (CPZ). Alcohol and LPS together induce M2b polarization of macrophages and promote the phosphorylation and nuclear translocation of P38, ERK1/2 and NF-κB, and could be inhibited by CPZ and NOD2 inhibitor. Thus, alcohol can aggravate experimental colitis in mice and promote macrophage M2b polarization through the TRPV1-MAPK/NF-kB pathways.

2023-07-24 | GSE237785 | GEO

Excess free fructose, apple juice, high fructose corn syrup and childhood asthma risk - the National Children's Study.

Project description:BackgroundRecent research provides consistent evidence that the unexplained doubling of childhood asthma prevalence (1980-1995), its continued climb and 2013 plateau, may be associated with the proliferation of high-fructose-corn-syrup (HFCS) in the US food supply. The HFCS used in soft drinks has been shown to contain a higher fructose-to-glucose ratio than previously thought. This coincides with a preference shift from orange to apple juice among young children. Apple juice naturally contains a high (?2:1) fructose-to-glucose ratio. Thus, children have received high excess-free-fructose doses, the fructose type associated with fructose malabsorption. Unabsorbed excess-free-fructose in the gut may react with dietary proteins to form immunogens that bind asthma mediating receptors, and/or alter the microbiota towards a profile linked to lung disorders. Studies with longitudinal childhood data are lacking. Therefore, we tested the hypothesis that excess-free-fructose intake is associated with childhood asthma risk.MethodsCox regression models were used to analyze prospective early childhood data (12-30?months of age) from the National Children's Study. Intake frequencies for soda/sports/fruit drinks, and 100% juices were used for analyses.ResultsGreater consumption of 100% juice, soda/sports/fruit drinks, and any combination, was associated with ~two (P?=?0.001), ~?2.5 (P?=?0.001), and?~?3.5 times (P?<?0.0001) higher asthma incidence.ConclusionsGiven these results, prior research and case-study evidence, it is reasonable to suggest that the two-fold higher asthma risk associated with 100% juice consumption is due to apple juice's high fructose-to-glucose ratio, and that the ~?2.5/~?3.5 times higher risk associated with soda/sports/fruit drinks intake is with the excess-free-fructose in HFCS.

| S-EPMC7313206 | biostudies-literature

High-Fructose Corn-Syrup-Sweetened Beverage Intake Increases 5-Hour Breast Milk Fructose Concentrations in Lactating Women.

Project description:This study determined the effects of consuming a high-fructose corn syrup (HFCS)-sweetened beverage on breast milk fructose, glucose, and lactose concentrations in lactating women. At six weeks postpartum, lactating mothers (n = 41) were randomized to a crossover study to consume a commercially available HFCS-sweetened beverage or artificially sweetened control beverage. At each session, mothers pumped a complete breast milk expression every hour for six consecutive hours. The baseline fasting concentrations of breast milk fructose, glucose, and lactose were 5.0 ± 1.3 µg/mL, 0.6 ± 0.3 mg/mL, and 6.8 ± 1.6 g/dL, respectively. The changes over time in breast milk sugars were significant only for fructose (treatment × time, p < 0.01). Post hoc comparisons showed the HFCS-sweetened beverage vs. control beverage increased breast milk fructose at 120 min (8.8 ± 2.1 vs. 5.3 ± 1.9 µg/mL), 180 min (9.4 ± 1.9 vs. 5.2 ± 2.2 µg/mL), 240 min (7.8 ± 1.7 vs. 5.1 ± 1.9 µg/mL), and 300 min (6.9 ± 1.4 vs. 4.9 ± 1.9 µg/mL) (all p < 0.05). The mean incremental area under the curve for breast milk fructose was also different between treatments (14.7 ± 1.2 vs. -2.60 ± 1.2 µg/mL × 360 min, p < 0.01). There was no treatment × time interaction for breast milk glucose or lactose. Our data suggest that the consumption of an HFCS-sweetened beverage increased breast milk fructose concentrations, which remained elevated up to five hours post-consumption.

| S-EPMC6024711 | biostudies-literature

Effects of high fructose corn syrup on intestinal microbiota structure and obesity in mice.

Project description:High fructose corn syrup (HFCS)-associated health problems have raised concerns. We investigated the effects of HFCS-containing drinking water on body fat, intestinal microbiota structure of mice, and the relationships between them. HFCS drinking water significantly increased body fat content and altered the intestinal microbiome. The Christensenellaceae R-7 group negatively correlated with body weight, perirenal fat, epididymal fat, and liver fat percentage.

| S-EPMC8891263 | biostudies-literature

Copper Metabolism Domain-Containing 1 Represses Genes That Promote Inflammation and Protects Mice From Colitis and Colitis-Associated Cancer

Project description:Background & Aims Activation of the transcription factor nuclear factor-κB (NF-κB) has been associated with the development of inflammatory bowel disease (IBD). Copper metabolism MURR1 domain containing 1 (COMMD1), a regulator of various transport pathways, has been shown to limit NF-κB activation. We investigated the roles of COMMD1 in the pathogenesis of colitis in mice and IBD in human beings.

2014-05-19 | GSE53368 | GEO

Diet-dependent gene expression in honey bees: honey vs. sucrose or high fructose corn syrup.

Project description:Severe declines in honey bee populations have made it imperative to understand key factors impacting honey bee health. Of major concern is nutrition, as malnutrition in honey bees is associated with immune system impairment and increased pesticide susceptibility. Beekeepers often feed high fructose corn syrup (HFCS) or sucrose after harvesting honey or during periods of nectar dearth. We report that, relative to honey, chronic feeding of either of these two alternative carbohydrate sources elicited hundreds of differences in gene expression in the fat body, a peripheral nutrient-sensing tissue analogous to vertebrate liver and adipose tissues. These expression differences included genes involved in protein metabolism and oxidation-reduction, including some involved in tyrosine and phenylalanine metabolism. Differences between HFCS and sucrose diets were much more subtle and included a few genes involved in carbohydrate and lipid metabolism. Our results suggest that bees receive nutritional components from honey that are not provided by alternative food sources widely used in apiculture.

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