Effects Of High Fructose Intake Research Articles

Effect of high-fructose consumption in pregnancy on the bone growth of offspring rats.

Growing evidence suggests that bone health is programmed in early life. Maternal diet may influence the skeletal development of offspring. We aimed to determine the possible effects of high-fructose intake during pregnancy on different aspects of long bone morphology in the offspring of rats and to initially explore the possible mechanisms. Pregnant Sprague-Dawley rats were randomly divided into four groups and intragastrically administered the same dose of distilled water (CON, n = 12), 20 g/kg/day glucose (GLU, n = 12), 10 g/kg/day fructose (LFRU, n = 12), or 20 g/kg/day fructose (HFRU, n = 12) for 21 days during gestation. Computed tomography was used to analyze the cortical and cancellous bones of the distal femur of the offspring rats, and circulating bone metabolic biomarkers were measured using enzyme immunoassay. The results showed that high-fructose intake during pregnancy could decrease body weight, impair glucose metabolism, and increase serum leptin and uric acid in offspring. The offspring in the HFRU group had higher levels of the N-terminal propeptide of type I procollagen (PINP) and the C-telopeptide of type I collagen (CTX). The bone mean density (BMD), the total cross-sectional area inside the periosteal envelope (Tt.Ar), cortical bone area (Ct.Ar), medullary (or marrow) area (Ma.Ar), and trabecular mean density of the offspring in the HFRU group were lower than those in the CON group. Tartrate-resistant acid phosphatase (Trap) staining showed that high-fructose intake during pregnancy could increase the number of osteoclasts and increase the absorption area. Our results suggested that excessive fructose intake during pregnancy could inhibit skeletal development in offspring. Thus, attention to fructose intake during pregnancy is important for bone development in offspring.

Short-Term High Fructose Intake Impairs Diurnal Oscillations in the Murine Cornea.

PurposeEndogenous and exogenous stressors, including nutritional challenges, may alter circadian rhythms in the cornea. This study aimed to determine the effects of high fructose intake (HFI) on circadian homeostasis in murine cornea.MethodsCorneas of male C57BL/6J mice subjected to 10 days of HFI (15% fructose in drinking water) were collected at 3-hour intervals over a 24-hour circadian cycle. Total extracted RNA was subjected to high-throughput RNA sequencing. Rhythmic transcriptional data were analyzed to determine the phase, rhythmicity, unique signature, metabolic pathways, and cell signaling pathways of transcripts with temporally coordinated expression. Corneas of HFI mice were collected for whole-mounted techniques after immunofluorescent staining to quantify mitotic cell number in the epithelium and trafficking of neutrophils and γδ-T cells to the limbal region over a circadian cycle.ResultsHFI significantly reprogrammed the circadian transcriptomic profiles of the normal cornea and reorganized unique temporal and clustering enrichment pathways, but did not affect core-clock machinery. HFI altered the distribution pattern and number of corneal epithelial mitotic cells and enhanced recruitment of neutrophils and γδ-T cell immune cells to the limbus across a circadian cycle. Cell cycle, immune function, metabolic processes, and neuronal-related transcription and associated pathways were altered in the corneas of HFI mice.ConclusionsHFI significantly reprograms diurnal oscillations in the cornea based on temporal and spatial distributions of epithelial mitosis, immune cell trafficking, and cell signaling pathways. Our findings reveal novel molecular targets for treating pathologic alterations in the cornea after HFI.

Effects of TNF-α antagonist infliximab on fructose-induced metabolic syndrome in rats.

Public health issues have been raised regarding fructose toxicity and its serious metabolic disorders. Deleterious effects of high fructose intake on insulin sensitivity, body weight, lipid homeostasis have been identified. The new millennium has witnessed the emergence of a modern epidemic, the metabolic syndrome (MS), in approximately 25% of the world's adult population. The current study aimed to investigate the effect of the TNF-α antagonist infliximab on fructose-induced MS in rats. Rats were administered fructose (10%) in drinking water for 12 weeks to induce the experimental MS model. infliximab (5 mg/kg) was injected once weekly intraperitoneally starting on the 13th week for 4 weeks. Increase in body weight, blood glucose level, serum triglycerides (TGs), adiponectin level and blood pressure were present in MS rats. They also prompted increases in serum of leptin, TNF-α, and malondialdehyde (MDA) levels. Treatment with infliximab did not affect body weight, hyperglycemia or hypertension, but decreased serum TGs and increased serum HDL-c levels. Infliximab also decreased adiponectin levels. Surprisingly, infliximab increased MDA above its value in the MS group. These results reflect the fact that infliximab affects the manifestations of MS in rats. Though infliximab reduced TGs, increased HDL-c levels, reversed adiponectin resistance occurred by fructose, the drug failed to combat MS-mediated hyperglycemia, hypertension, and elevated MDA above the insult.

Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer

Harmful effects of high fructose intake on health have been widely reported. Although fructose is known to promote cancer, little is known about the underlying mechanisms. Here, we found that fructose triggers breast cancer metastasis through the ketohexokinase-A signaling pathway. Molecular experiments showed that ketohexokinase-A, rather than ketohexokinase-C, is necessary and sufficient for fructose-induced cell invasion. Ketohexokinase-A-overexpressing breast cancer was found to be highly metastatic in fructose-fed mice. Mechanistically, cytoplasmic ketohexokinase-A enters into the nucleus during fructose stimulation, which is mediated by LRRC59 and KPNB1. In the nucleus, ketohexokinase-A phosphorylates YWHAH at Ser25 and the YWHAH recruits SLUG to the CDH1 promoter, which triggers cell migration. This study provides the effect of nutrition on breast cancer metastasis. High intake of fructose should be restricted in cancer patients to reduce the risk of metastasis. From a therapeutic perspective, the ketohexokinase-A signaling pathway could be a potential target to prevent cancer metastasis.

Suppression of uric acid and lactate production by sodium acetate ameliorates hepatic triglyceride accumulation in fructose-insulin resistant pregnant rats

High fructose intake has been associated with perturbed lipid, uric acid and lactate homeostasis. However, consumption of fructose-sweetened beverages is not usually regulated during pregnancy. The effect of short-chain fatty acid (acetate) on the metabolic effects of high fructose intake during pregnancy is not known. We hypothesized that acetate prevents gestational fructose-induced hepatic triglyceride (TG) accumulation by suppressing uric acid and lactate production. Pregnant Wistar rats were randomly separated into three groups (n = 6/group) receiving drinking water (CON), 10 % (w/v) fructose drink (FRU) and 10 % (w/v) fructose with 200 mg/kg (w/w; p.o.) sodium acetate (FRU + ACE) daily for nineteen days. Fructose intake resulted in increased body weight gain, liver weight, fluid intake, visceral fat, insulin resistance, fasting blood glucose, insulin, plasma and hepatic TG, total cholesterol, free fatty acid, lipid peroxidation, adenosine deaminase, xanthine oxidase, uric acid, lactate, lactate dehydrogenase, and liver injury marker enzymes. However, gestational high fructose intake led to depressed plasma and hepatic glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant barrier, adenosine and food intake. All these effects except water intake and food intake were abated by sodium acetate. These results demonstrate that maternal fructose-enriched drink would cause hepatic TG accumulation that is associated with perturbed glucose, uric acid, lactate homeostasis, and G6PD-dependent antioxidant barrier. These results also demonstrate that acetate protects the liver against gestational fructose-induced TG accumulation by inhibiting uric acid and lactate production. Thus, acetate may be useful in the treatment of hyperuricemia- and hyperlactatemia-related disorders.

Effects of high fructose intake on liver injury progression in high fat diet induced fatty liver disease in ovariectomized female mice

Epidemiology shows that the morbidity of nonalcoholic fatty liver disease (NAFLD) is increased in postmenopausal women and chronic high fructose intake induces NAFLD progression. To analyze the effects of high fructose intake on estrogen deficiency, we evaluated liver disease progression using ovariectomized mice fed with a high fat diet (HFD) for 12 weeks. Hepatic steatosis developed in all HFD groups. Fructose intake significantly increased the liver weight and serum alanine aminotransferase, which was not exacerbated by ovariectomy alone. Ovariectomy enhanced the hepatic inflammatory activity shown by tumor necrosis factor α upregulation in the groups with or without fructose intake. Both fructose intake and ovariectomy increased the hepatocytes with ballooning degeneration and hepatic macrophage infiltration and activated hepatic stellate cells. Coexistence of fructose intake and ovariectomy markedly enhanced liver cell destruction, macrophage accumulation, and progression of fibrosis. Liver damage was ameliorated by 17β-estradiol supplementation. These findings suggest that high fructose intake enhanced the progression of NAFLD in ovariectomized female mice.

High fructose diet feeding accelerates diabetic nephropathy in Spontaneously Diabetic Torii (SDT) rats.

Diabetic nephropathy (DN) is one of the complications of diabetes and is now the most common cause of end-stage renal disease. Fructose is a simple carbohydrate that is present in fruits and honey and is used as a sweetener because of its sweet taste. Fructose has been reported to have the potential to progress diabetes and DN in humans even though fructose itself does not increase postprandial plasma glucose levels. In this study, we investigated the effects of high fructose intake on the kidney of the Spontaneously Diabetic Torii (SDT) rats which have renal lesions similar to those in DN patients and compared these with the effects in normal SD rats. This study revealed that a 4-week feeding of the high fructose diet increased urinary excretion of kidney injury makers for tubular injury and accelerated mainly renal tubular and interstitial lesions in the SDT rats but not in normal rats. The progression of the nephropathy in the SDT rats was considered to be related to increased internal uric acid and blood glucose levels due to the high fructose intake. In conclusion, high fructose intake exaggerated the renal lesions in the SDT rats probably due to effects on the tubules and interstitium through metabolic implications for uric acid and glucose.

The expression of MYC regulates cellular proliferation and apoptosis through TGF-beta receptor dependent manner

Epidemiology shows that the morbidity of nonalcoholic fatty liver disease (NAFLD) is increased in postmenopausal women and chronic high fructose intake induces NAFLD progression. To analyze the effects of high fructose intake on estrogen deficiency, we evaluated liver disease progression using ovariectomized mice fed with a high fat diet (HFD) for 12 weeks. Hepatic steatosis developed in all HFD groups. Fructose intake significantly increased the liver weight and serum alanine aminotransferase, which was not exacerbated by ovariectomy alone. Ovariectomy enhanced the hepatic inflammatory activity shown by tumor necrosis factor α upregulation in the groups with or without fructose intake. Both fructose intake and ovariectomy increased the hepatocytes with ballooning degeneration and hepatic macrophage infiltration and activated hepatic stellate cells. Coexistence of fructose intake and ovariectomy markedly enhanced liver cell destruction, macrophage accumulation, and progression of fibrosis. Liver damage was ameliorated by 17β-estradiol supplementation. These findings suggest that high fructose intake enhanced the progression of NAFLD in ovariectomized female mice.

Deleterious Metabolic Effects of High Fructose Intake: The Preventive Effect of Lactobacillus kefiri Administration

Modern lifestyle and diets have been associated with metabolic disorders and an imbalance in the normal gut microbiota. Probiotics are widely known for their health beneficial properties targeting the gut microbial ecosystem. The aim of our study was to evaluate the preventive effect of Lactobacillus kefiri (L. kefiri) administration in a fructose-rich diet (FRD) mice model. Mice were provided with tap water or fructose-added (20% w/v) drinking water supplemented or not with L. kefiri. Results showed that probiotic administration prevented weight gain and epidydimal adipose tissue (EAT) expansion, with partial reversion of the adipocyte hypertrophy developed by FRD. Moreover, the probiotic prevented the increase of plasma triglycerides and leptin, together with the liver triglyceride content. Leptin adipocyte secretion was also improved by L. kefiri, being able to respond to an insulin stimulus. Glucose intolerance was partially prevented by L. kefiri treatment (GTT) and local inflammation (TNFα; IL1β; IL6 and INFγ) was completely inhibited in EAT. L. kefiri supplementation generated an impact on gut microbiota composition, changing Bacteroidetes and Firmicutes profiles. Overall, our results indicate that the administration of probiotics prevents the deleterious effects of FRD intake and should therefore be promoted to improve metabolic disorders.

Effects of high fructose intake on the development of hypertension in the spontaneously hypertensive rats: the role of AT1R/gp91PHOX signaling in the rostral ventrolateral medulla

Both genetic and dietary factors determine the development of hypertension. Whether dietary factor impacts the development of hereditary hypertension is unknown. Here, we evaluated the effect of daily high-fructose diet (HFD) on the development of hypertension in adolescent spontaneously hypertensive rats (SHR). Six-week-old SHR were randomly divided into two groups to receive HFD or normal diet (ND) for 3 weeks. The temporal profile of systolic blood pressure, alongside the sympathetic vasomotor activity, in the SHR-HFD showed significantly greater increases at 9–12 weeks of age compared with the age-matched SHR-ND group. Immunofluorescence was used to identify the distribution of reactive oxygen species (ROS), oxidants and antioxidants in rostral ventrolateral medulla (RVLM) where sympathetic premotor neurons reside. In RVLM of SHR-HFD, the levels of ROS accumulation and lipid peroxidation were elevated. The changes in protein expression were measured by Western blot. NADPH oxidase subunit gp91phox and angiotensin II type I receptor were up-regulated in RVLM neuron. On the other hand, the expression of extracellular superoxide dismutase was suppressed. Both molecular and hemodynamic changes in the SHR-HFD were rescued by oral pioglitazone treatment from weeks 7 to 9. Furthermore, central infusion with tempol, a ROS scavenger, effectively ameliorated ROS accumulation in RVLM and diminished the heightened pressor response and enhanced sympathetic activity in the SHR-HFD. Together, these results suggest that HFD intake at adolescent SHR may impact the development of hypertension via increasing oxidative stress in RVLM which could be effectively attenuated by pioglitazone treatment.

PPARβ/δ ameliorates fructose-induced insulin resistance in adipocytes by preventing Nrf2 activation

We studied whether PPARβ/δ deficiency modifies the effects of high fructose intake (30% fructose in drinking water) on glucose tolerance and adipose tissue dysfunction, focusing on the CD36-dependent pathway that enhances adipose tissue inflammation and impairs insulin signaling. Fructose intake for 8weeks significantly increased body and liver weight, and hepatic triglyceride accumulation in PPARβ/δ-deficient mice but not in wild-type mice. Feeding PPARβ/δ-deficient mice with fructose exacerbated glucose intolerance and led to macrophage infiltration, inflammation, enhanced mRNA and protein levels of CD36, and activation of the JNK pathway in white adipose tissue compared to those of water-fed PPARβ/δ-deficient mice. Cultured adipocytes exposed to fructose also exhibited increased CD36 protein levels and this increase was prevented by the PPARβ/δ activator GW501516. Interestingly, the levels of the nuclear factor E2-related factor 2 (Nrf2), a transcription factor reported to up-regulate Cd36 expression and to impair insulin signaling, were increased in fructose-exposed adipocytes whereas co-incubation with GW501516 abolished this increase. In agreement with Nrf2 playing a role in the fructose-induced CD36 protein level increases, the Nrf2 inhibitor trigonelline prevented the increase and the reduction in insulin-stimulated AKT phosphorylation caused by fructose in adipocytes. Protein levels of the well-known Nrf2 target gene NAD(P)H:quinone oxidoreductase 1 (Nqo1) were increased in water-fed PPARβ/δ-null mice, suggesting that PPARβ/δ deficiency increases Nrf2 activity; and this increase was exacerbated in fructose-fed PPARβ/δ-deficient mice. These findings indicate that the combination of high fructose intake and PPARβ/δ deficiency increases CD36 protein levels via Nrf2, a process that promotes chronic inflammation and insulin resistance in adipose tissue.

Fructose feeding changes taurine homeostasis in wistar rats.

High-fructose intake has been shown to induce dyslipidemia and other hallmarks of the metabolic syndrome and taurine seems able to ameliorate these effects. However, the effects of high fructose intake on taurine homeostasis are currently unknown. Here we examined the effects of a high-fructose diet with or without oral taurine supplementation (2 % in drinking water) for 6 weeks in Wistar rats.