Fructose Consumption Research Articles

Derangement of metabolic homeostasis, detoxifying ability and CA 15-3 in young adult female rats by fructose (15%) drinking is akin to known carcinogens: A missed fiend?

Objectives: Breast cancer (BC) has been the bane of peri-and post-menopausal women, but is now increasingly incident in adolescent/young adult (AYA) females. Pari-passu, there has been a >1000% increase in consumption of fructose as a caloric sweetener in soft drinks, whose top consumers are AYAs. The link between fructose consumption and mammary gland (MG) carcinogenesis is not well-established and the same is investigated and compared against known carcinogens such as 7,12-dimethylbenz(a)anthracene (DMBA) and electromagnetic radiations from mobile phone (EMF-MP). Materials and Methods: Weaned female Wistar rats were randomly grouped as normal control (NOR), fructose control (FRC), DMBA control (DMC), and exposure control (EXC). For 8 weeks, the NOR was provided chow and water, ad libitum, while FRC, DMC, and EXC additionally received 15% fructose drinking solution, ad libitum, DMBA (20 mg/Kg, p.o; at weaning) and EMF-MP (Global System for Mobile Communications [GSM]), 2 h/day daily), respectively. At the end of the study, the groups were compared for the biomarkers of insulin resistance (IR), carbohydrate and lipid metabolism, liver function, cardiometabolic function, oxidative stress, and MG carcinogenesis. Results: The serum markers of MG carcinogenesis (CA 15–3), IR (homeostasis model assessment-IR, area under the curve – oral glucose tolerance test), and liver and cardiometabolic function (serum glutamicoxaloacetic transaminase and homocysteine) were significantly raised (P < 0.05) in FRC versus NOR. The metabolic homeostasis (leptin, ghrelin, triglyceride-Glucose index, glucose-6-phosphatase, triglyceride, high-density lipoprotein, serum glutamic pyruvic transaminase, alkaline phosphatase, and glycogen) and detoxifying ability (free-radical scavenging activity [%] and superoxide dismutase) in FRC were not different from DMC, or EXC. Conclusion: The development of early indicators of MG carcinogenesis due to unhindered fructose drinking by AYA female rats is akin to exposure to DMBA or EMF-MPs that evidence the propensity of the former.

FRI029 Chronic Free Fatty Acid Elevation Is Associated With An Overcompensatory Increase In Hepatic Mitochondrial Function In Patients With Overweight Or Obesity

Abstract Disclosure: F. Bril: None. S. Kalavalapalli: None. K. Cusi: None. The obesity epidemic has resulted in a significant increase in the prevalence of nonalcoholic fatty liver disease (NAFLD). Some patients with NAFLD progress to more severe forms of the disease, such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Our central hypothesis is that the inability of hepatic mitochondria to enhance nutrient oxidation in the setting of nutrient oversupply plays a key role in the progression of NAFLD. Specifically, the aim of this study was to assess if free fatty acid (FFA) excess contributes to hepatic mitochondrial dysfunction in patients with overweight or obesity. Patients with BMI ≥ 25kg/m2, without diabetes were included in the study. Patients underwent a 2-hour oral glucose tolerance test (OGTT) and a liver proton magnetic resonance spectroscopy (1H-MRS) to measure liver fat. In vivo hepatic mitochondrial ATP levels were measured by phosphorus (31P)-MRS every 30 minutes during a 2-hour oral fructose challenge (OFC). Due to unregulated phosphorylation of fructose upon entering hepatocytes, the OFC provides a dynamic measurement of hepatic ATP consumption and re-synthesis. Hepatic ATP levels were estimated as β-ATP/total phosphorus. A total of 37 patients were recruited for this study (age: 54 ± 11 years; sex: 43% male/57% female; BMI: 34.4 ± 6.3 kg/m2; A1c: 5.7 ± 0.4%; NAFLD: 51%). No differences were found in hepatic ATP levels in patients with or without NAFLD (0.019 ± 0.015 vs. 0.016 ± 0.012, p=0.44). Patients were then divided in three groups (tertiles) based on fasting FFA levels. We did not observe any significant differences among these three groups in key clinical variables, such as age, sex, BMI, A1c or prevalence of NAFLD. At baseline (pre OFC), we did not observe any difference in hepatic ATP levels (i.e., β-ATP/total phosphorus) among FFA tertiles (0.020 ± 0.015, 0.020 ± 0.012, and 0.012 ± 0.012, p=0.25). During the OFC, we estimated changes over time in hepatic ATP levels as the decremental area under the curve (AUROC) of β-ATP/total phosphorus. We observed that the decremental AUROC of hepatic ATP levels during OFC was significantly different among groups (0.57 ± 0.86, 0.14 ± 0.59, -0.40 ± 0.54, p=0.006). Patients in the highest tertile of FFAs showed no consumption of ATP after the OFC, but rather an overall increase in ATP AUROC over time. Plasma FFA levels correlated well with hepatic ATP AUROC during the OFC (-0.47, p =0.007). Conclusion: Chronic elevations in FFA levels are associated with changes in hepatic mitochondrial ATP synthesis, which were unmasked after an oral fructose challenge. While long-term, FFA elevations may impair mitochondrial function, in our study we observed an overcompensatory response in patients with high plasma FFA, characterized by an increase in hepatic ATP levels over time after fructose consumption. At what point this compensation is overwhelmed leading to inflammation and cellular lipotoxicity remains to be determined. Presentation: Friday, June 16, 2023

Transcriptome analysis of the effects of maternal fructose exposure during gestation and lactation on the cytoskeleton of offspring hippocampus

Excessive fructose consumption poses a public health concern. Maternal fructose overconsumption impairs offspring hippocampal function, indicating hippocampal sensitivity to fructose. The hippocampus is the vital for spatial learning and memory, and the cytoskeletal structure is crucial for hippocampal neuronal plasticity. The Rho GTPase is a key regulator of neuronal cytoskeleton formation, with RhoA protein governing neuronal growth and development. The RhoA/ROCK2 pathway affects myosin light chain phosphorylation, leading to cytoskeletal reorganization, actin cytoskeleton changes, and neurite retraction. However, the effects of maternal fructose exposure during gestation and lactation on the offspring's neural cytoskeleton remain unclear. We established maternal fructose exposure models during gestation and lactation, assessing fasting blood glucose levels in offspring confirm model effectiveness. Whole transcriptome sequencing examined offspring hippocampal developmental programming. Immunofluorescence and Western blot analyses assessed RhoA/ROCK2 pathway expression changes in the hippocampus, with PCR validating transcriptome sequencing results. Transcriptome sequencing identified 193 and 298 differentially expressed genes in the control, 13% fructose, and 40% fructose groups, respectively. GO and KEGG analyses revealed significant changes related to neural development, learning memory, and cytoskeleton in both fructose-exposed groups. GSEA indicated substantial cytoskeleton-related alterations in the offspring. Immunofluorescence demonstrated significant CRMP2 protein down-regulation in both fructose-exposed groups. Western blotting showed significantly higher expression of RhoA, ROCK2, p-ROCK2, and p-MLC2 in the fructose-exposed groups (P < 0.05). Maternal high-fructose exposure significantly impacts gene expression in offspring. These alterations may influence hippocampal neurodevelopment by up-regulating the RhoA/ROCK2 pathway, leading to cytoskeletal damage and axon growth inhibition.

The chronic consumption of dietary fructose promotes the gut Clostridium species imbalance and bile acid alterations in developing nonalcoholic fatty liver disease

Excessive fructose intake is associated with the rising prevalence of nonalcoholic fatty liver disease (NAFLD). The gut microbiome (GM) and bile acids (BAs) are involved in the pathogenesis of NAFLD, but the impact of fructose on their cross-talk is unclear. In this study, adult male C57BL/6J mice were fed a normal diet with tap water (ND) or with 4% fructose in the drinking water (Fru), 60% high-fat diet with tap water (HF) or with 4% fructose solution (HFF) for 12 weeks. Targeted BA analysis was performed in five anatomical sites including the liver, ileum contents, portal serum, cecum contents, and feces. Metagenomic sequencing was performed to explore gut dysbiosis. Within 12 weeks, the 4% fructose diet could initially stimulate gut dysbiosis and BA upregulation in the ileum, portal serum, and cecum when the intestinal and hepatic transport system remained stable without hepatic lipid accumulation. However, the chronic consumption of fructose promoted HF-induced NAFLD, with significantly increased body weight, impaired glucose tolerance, and advanced liver steatosis. BA transporters were inhibited in HFF, causing the block of internal BA circulation and increased BA secretion via cecum contents and feces. Notably, lithocholic acid (LCA) and its taurine conjugates were elevated within the enterohepatic circulation. Meanwhile, the Clostridium species were significantly altered in both Fru and HFF groups and were closely associated with fructose and BA metabolism. In summary, excessive fructose caused gut dysbiosis and BA alterations, promoting HF-induced NAFLD. The crosstalk between Clostridium sp. and LCA species were potential targets in fructose-mediated NAFLD.

Abstract 107: Longitudinal Associations Of Dietary Fructose And Psychological Stress With Vascular Aging Index And Incident Cardiovascular Disease Among Us Black And White Adults In The CARDIA Study

Background: Cardiovascular diseases (CVD) is the leading cause of death and disability worldwide. CVD risk increases exponentially with age, largely due to pathophysiological changes within the vasculature. As per AHA’s Life’s Essential 8, modifiable lifestyle factors such as diet and psychological stress are important predictors of CVD. We designed this study to assess how dietary behaviors, specifically sucrose, fructose and sodium, and endured psychological stress in young adult men and women impact the vascular aging index (VAI) and CVD risk by mid-life. Methods: All data were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. We used the data from black and white men and women (n=2656) who had undergone carotid artery ultrasound Doppler scans at visit 7 (year 20 of follow-up) and used these measures to calculate the VAI, as shown previously. Baseline demographics, dietary data and stress/depression measures (CES-D scores) were obtained from visits 1 (at enrollment, year 0) and 7 and compared (men vs. women) with Kruskal-Wallis and Pearson’s chi-square tests. Regression analyses were used to assess the predictive value of these variables on VAI. Cox regression analyses were conducted to assess the risk of fatal and non-fatal CVD, hypertensive CVD, and stroke. Results: Significant associations were found for fructose intake (expressed as percent total calories, P=0.042) and BP &gt;30/80 mmHg (P=0.025) at baseline with VAI in men but not women. Conversely, CES-D scores at baseline were significantly associated with VAI in women (P=0.014) but not men. On Cox regression analyses, baseline BMI was significantly associated with the incidence of any CVD (HR=1.065, P &lt;0.001), hypertensive CVD (HR=1.083, P&lt;0.001) and stroke (HR=1.068, P=0.002) 30 years later. Dietary fructose intake recorded in mid-life was significantly associated with the incidence of any CVD (HR=1.041, P=0.044), and having BP &gt;130/80 mmHg at baseline was associated with stroke (HR=1.996, P=0.029). No sex differences were noted in the Cox regression analyses. Conclusion: Our results suggest that in young adult black and white men but not women BMI and fructose consumption, but not sodium are associated with increased VAI and incidence of CVD by mid-life.

Associations of Dietary Fructose and Sucrose Intake with HbA1c and Anthropometric Measurements in Patients with Type 2 Diabetes Mellitus

Aim. This study aimed to evaluate the associations of daily dietary intake of fructose and sucrose with HbA1c levels and anthropometric measurements in patients with Type 2 diabetes mellitus.&#x0D; Methods. A total of 64 individuals were included in the study. Demographic characteristics, eating habits, frequency of fructose and sucrose source consumption, and dietary intakes were assessed through questioning. Anthropometric measurements, including body weight, height circumference (HtC), waist circumference (WC), hip circumference (HC), neck circumference (NC), wrist circumference (WrC), and mid-upper arm circumference (MUAC), were evaluated. The HbA1c level was categorized into two groups: good glycemic control (HbA1c≤ 7%) and poor (HbA1c&gt; 7%) glycemic control.&#x0D; Results. The mean daily fructose and sucrose intakes were 10.57 ± 8.28 g (2.38 ± 1.96%), and 29.21 ± 24.78 g (6.29 ± 5.35%), respectively. All the anthropometric measurements assessed were lower in the group with good glycemic control; however, only in case of BMI, MUAC, NC, and WrC, these differences were significant. Patients with good glycemic control were found to consume more fruit. Anthropometric measurements were not related to daily fructose intake, but positively associated with sucrose intake and HbA1c levels. Specifically, HbA1c levels were negatively associated with fiber intake and positively associated with sucrose intake. Moreover, HbA1c levels were positively affected by NC and consumption of non-alcoholic carbonated drinks, and negatively affected by WC and consumption of sugar-containing instant coffee.&#x0D; Conclusions. The mean daily fructose intake among diabetics was found to be moderate and sucrose intake was consistent with the recommended range. The level of HbA1c was shown to be associated with all the anthropometric parameters assessed, and it was found that sugar-sweetened beverages could affect the level of HbA1c. However, further studies with larger sample sizes are needed to investigate these relationships more comprehensively.

Association of Diet Consumption with Gallbladder Changes in Females After Birth of Child

The postpartum period is characterized by remarkable physiological adaptations to accommodate the demands of childbirth and lactation. These physiological changes, coupled with the unique nutritional needs of both the mother and newborn, can lead to gallbladder stasis and increased cholesterol absorption in the gallbladder. Objective: To assess the correlation between diet consumption and gallbladder changes in females after childbirth. Methods: This observational study was conducted at the department of Gastroenterology, Jinnah Medical and Dental College, Sohail University, Karachi, Pakistan from December 2022 to June 2022. Females of reproductive age who had normal child delivery were evaluated after 6 weeks of delivery. The medical examination, anthropometric measures, nutritional assessment, and laboratory testing were performed in all eligible females. An ultrasonographic was done after a typical fatty food in order to assess gallbladder changes. SPSS version 21.0 was used to do statistically analysis. Results: The mean age was 28.89 ± 4.73 and mean BMI was 22.78 ± 4.09 kg/m2. Of 100 females, 17% had gallbladder stasis, 26% had gallstones, and 17% had sludge. The females with low protein consumption had significantly higher proportion of gallbladder stasis as compared to females with high protein consumption in diet (76.5% vs 23.5%, p=0.001). Furthermore, females with high carbohydrate (61.5% vs 38.5%, p=0.011) and fructose (53.8% vs 46.2%, p=0.037) consumption had significantly higher proportion of gallstones as compared to females with low consumption. Conclusions: High protein consumption was linked to gallbladder stasis, while high carbohydrate and fructose intake were associated with an increased proportion of gallstones.

Morroniside Delays NAFLD Progression in Fructose-Fed Mice by Normalizing Lipid Metabolism and Inhibiting the Inflammatory Response

Chronic fructose consumption is becoming one leading risk factor for NAFLD due to its hazard on cellular lipid metabolism, which plays an essential role in the pathogenesis of NAFLD. Morroniside, an iridoid glycoside from Cornus officinalis, has been suggested to have potent in regulating cellular glucolipid metabolism. However, the effect and mechanism of morroniside on improving fructose-induced hepatic steatosis and retarding NAFLD progression remain ambiguous. In this study, we illustrate the efficacy of morroniside in alleviating fructose-triggered hepatic steatosis in mice. Mechanically, morroniside suppressed de novo lipogenesis and promoted β-oxidation by inhibiting the activation of PGC1β. Additionally, morroniside was found to work in attenuating hepatic inflammation in response to long-term fructose intake. Taken together, the current study reveals that morroniside is a promising food and medicinal therapy for NAFLD treatment and is effective in delaying the progression of NAFLD to NASH, especially in subtypes caused by excessive carbohydrate intake.

Fructose consumption during pregnancy increases intestinal cholesterol absorption in rat male descendants treated with a high-fructose high-cholesterol diet

Fructose consumption during pregnancy increases intestinal cholesterol absorption in rat male descendants treated with a high-fructose high-cholesterol diet

Diversity of Indigenous Saccharomyces cerevisiae Yeast Strains in Cabernet Sauvignon Fermentations from Utiel-Requena Region (Spain) as a Resource to Improve Wine Distinctiveness

The aim of this study was to isolate and characterize autochthonous Saccharomyces cerevisiae yeasts from Cabernet Sauvignon grape must and to analyze how they impacted the final characteristics of the wines obtained from the same type of must. This work was carried out in a “Pago” winery located in Requena, Spain. Twenty-two isolates were obtained from grape must. After molecular identification and typing, 11 different strains were determined. Growth-related parameters and metabolic characteristics (glucose and fructose consumption and ethanol, glycerol and acetic acid production) were determined via laboratory-scale fermentations (50 mL) of Cabernet Sauvignon must. From 2 L fermentation batches, the residual sugar, density, ethanol concentration, titratable and volatile acidities, pH and polyphenolic and volatile compounds were determined, as well as the sensory attributes of the produced wines. Differences between strains in the growth and metabolic parameters were observed. Eleven S. cerevisiae strain profiles were characterized to establish which strain or strains of the selected yeasts would produce the highest polyphenolic and aromatic concentrations of the red Cabernet wines made in the “Pago winery”, to then multiply them for their use to make the red wines of this winery.

6-Methyl flavone inhibits Nogo-B expression and improves high fructose diet-induced liver injury in mice.

Excessive fructose consumption increases hepatic de novo lipogenesis, resulting in cellular stress, inflammation and liver injury. Nogo-B is a resident protein of the endoplasmic reticulum that regulates its structure and function. Hepatic Nogo-B is a key protein in glycolipid metabolism, and inhibition of Nogo-B has protective effects against metabolic syndrome, thus small molecules that inhibit Nogo-B have therapeutic benefits for glycolipid metabolism disorders. In this study we tested 14 flavones/isoflavones in hepatocytes using dual luciferase reporter system based on the Nogo-B transcriptional response system, and found that 6-methyl flavone (6-MF) exerted the strongest inhibition on Nogo-B expression in hepatocytes with an IC50 value of 15.85 μM. Administration of 6-MF (50 mg· kg-1 ·d-1, i.g. for 3 weeks) significantly improved insulin resistance along with ameliorated liver injury and hypertriglyceridemia in high fructose diet-fed mice. In HepG2 cells cultured in a media containing an FA-fructose mixture, 6-MF (15 μM) significantly inhibited lipid synthesis, oxidative stress and inflammatory responses. Furthermore, we revealed that 6-MF inhibited Nogo-B/ChREBP-mediated fatty acid synthesis and reduced lipid accumulation in hepatocytes by restoring cellular autophagy and promoting fatty acid oxidation via the AMPKα-mTOR pathway. Thus, 6-MF may serve as a potential Nogo-B inhibitor to treat metabolic syndrome caused by glycolipid metabolism dysregulation.

Lipid peroxidation and neuroinflammation: A possible link between maternal fructose intake and delay of acquisition of neonatal reflexes in Wistar female rats.

Fructose is a common sweetener found in the daily diet supplemented to many processed and ultra-processed foods and beverages. Consumption of fructose-sweetened beverages has drastically increased in the last decades and is widely associated with metabolic disease, systemic pro-inflammatory status, and adverse transgenerational effects. To date, the impact of maternal fructose intake in brain function of the offspring is less explored. Therefore, the aim of this study was first, to investigate adverse effects in developmental milestones of the progeny of mothers with metabolic syndrome (MetS), induced by ad libitum consumption of a 20% fructose solution, and second to identify possible molecular changes in the nervous system of the newborns associated with maternal fructose intake. Wistar rats were randomly separated into two groups with access to water or fructose (20% w/v in water) for 10 weeks. After MetS was confirmed, dams were mated with control males and continued drinking water or fructose solution during gestation. At postnatal day (PN) 1, a subgroup of offspring of each sex was sacrificed and brains were dissected for oxidative stress and inflammatory status analysis. Changes in the developmental milestones due to maternal fructose consumption were studied (PN3-PN21) in another subgroup of offspring. Sexually dimorphic effects were found on the progeny's acquisition of neurodevelopmental milestones, in brain lipid peroxidation, neuroinflammation, and antioxidative defensive response. Our results suggest that dams' MetS, induced by fructose intake, disrupts brain redox homeostasis in female offspring and affects sensorimotor brain circuitry which may have a translational value for studying neurodevelopmental diseases.

830-P: Preclinical Development of ALN-KHK, an Investigational RNAi Therapeutic for Type 2 Diabetes Mellitus

Fructose consumption is implicated in increased rates of metabolic syndrome and type 2 diabetes worldwide. In the liver, ketohexokinase (KHK) is required for fructose metabolism, phosphorylating fructose to fructose-1-phosphate (F1P), a substrate for synthesis of fatty acids, contributing to nonalcoholic fatty liver. Excess liver fat is associated with insulin resistance and loss of glycemic control. Lowering KHK expression should reduce fatty acid synthesis and thus reduce insulin resistance and improve glycemic control in obese individuals with T2DM. We developed a robust RNAi therapeutics platform for delivery of siRNAs to liver using GalNAc conjugates to specifically silence hepatocyte-expressed genes. Liver-directed silencing of KHK improved insulin sensitivity in pre-clinical models of T2DM. ALN-KHK was selected based on in vitro assessment of a large set of GalNAc-siRNAs targeting human and primate KHK. ALN-KHK demonstrated suppression of liver KHK mRNA and protein in cynomolgus macaques after a single subcutaneous (SC) injection with potent and durable reduction in KHK protein (94.1% lowering through day 85 at the 10 mg/kg dose) supporting evaluation of infrequent dosing in the clinic. To evaluate impact of KHK silencing on fructose metabolism and establish circulating biomarkers of pharmacology, cynomolgus macaques were administered an oral fructose bolus on Day 30 following SC injection of ALN-KHK of 0.3, 3 or 10 mg/kg. ALN-KHK treatment resulted in a dose-dependent increase in circulating fructose with a 4.6-fold increase and a 10.7-fold decrease in FGF21 (which is regulated by liver F1P), at 2 hr post fructose bolus, associated with 90.7% KHK liver protein reduction. These data suggest monitoring of circulating fructose and FGF21 to assess KHK silencing in the clinic. In IND-enabling rat and non-human primate toxicology studies ALN-KHK was safe and well tolerated, supporting the planned initiation of first-in-human studies in obese healthy volunteers. Disclosure L. Noetzli: Employee; Alnylam Pharmaceuticals, Inc. Stock/Shareholder; Alnylam Pharmaceuticals, Inc. A. Borodovsky: Employee; Alnylam Pharmaceuticals, Inc. Stock/Shareholder; Alnylam Pharmaceuticals, Inc. X. Chua: Employee; Alnylam Pharmaceuticals, Inc. Stock/Shareholder; Alnylam Pharmaceuticals, Inc. R. Tymon: Employee; Alnylam Pharmaceuticals, Inc. Stock/Shareholder; Alnylam Pharmaceuticals, Inc. J. Darcy: None. S. Belozerova: Employee; Alnylam Pharmaceuticals, Inc. Stock/Shareholder; Alnylam Pharmaceuticals, Inc. M. Keibler: Employee; Alnylam Pharmaceuticals, Inc. Stock/Shareholder; Alnylam Pharmaceuticals, Inc. H. Tu: Employee; Alnylam Pharmaceuticals, Inc. Stock/Shareholder; Alnylam Pharmaceuticals, Inc. E. Maratos-Flier: Employee; Novartis, Alnylam Pharmaceuticals, Inc.

Effects of Fructose and Palmitic Acid on Gene Expression in Drosophila melanogaster Larvae: Implications for Neurodegenerative Diseases.

One of the largest health problems worldwide is the development of chronic noncommunicable diseases due to the consumption of hypercaloric diets. Among the most common alterations are cardiovascular diseases, and a high correlation between overnutrition and neurodegenerative diseases has also been found. The urgency in the study of specific damage to tissues such as the brain and intestine led us to use Drosophila melanogaster to study the metabolic effects caused by the consumption of fructose and palmitic acid in specific tissues. Thus, third instar larvae (96 ± 4 h) of the wild Canton-S strain of D. melanogaster were used to perform transcriptomic profiling in brain and midgut tissues to test for the potential metabolic effects of a diet supplemented with fructose and palmitic acid. Our data infer that this diet can alter the biosynthesis of proteins at the mRNA level that participate in the synthesis of amino acids, as well as fundamental enzymes for the dopaminergic and GABAergic systems in the midgut and brain. These also demonstrated alterations in the tissues of flies that may help explain the development of various reported human diseases associated with the consumption of fructose and palmitic acid in humans. These studies will not only help to better understand the mechanisms by which the consumption of these alimentary products is related to the development of neuronal diseases but may also contribute to the prevention of these conditions.

Exogenous gibberellin delays maturation in persimmon fruit through transcriptional activators and repressors.

As the harvest season of most fruit is concentrated, fruit maturation manipulation is essential for the fresh fruit industry to prolong sales time. Gibberellin (GA), an important phytohormone necessary for plant growth and development, has also shown a substantial regulatory effect on fruit maturation; however, its regulatory mechanisms remain inconclusive. In this research, preharvest GA3 treatment effectively delayed fruit maturation in several persimmon (Diospyros kaki) cultivars. Among the proteins encoded by differentially expressed genes, 2 transcriptional activators (NAC TRANSCRIPTION FACTOR DkNAC24 and ETHYLENE RESPONSIVE FACTOR DkERF38) and a repressor (MYB-LIKE TRANSCRIPTION FACTOR DkMYB22) were direct regulators of GERANYLGERANYL DIPHOSPHATE SYNTHASE DkGGPS1, LYSINE HISTIDINE TRANSPORTER DkLHT1, and FRUCTOSE-BISPHOSPHATE ALDOLASE DkFBA1, respectively, resulting in the inhibition of carotenoid synthesis, outward transport of an ethylene precursor, and consumption of fructose and glucose. Thus, the present study not only provides a practical method to prolong the persimmon fruit maturation period in various cultivars but also provides insights into the regulatory mechanisms of GA on multiple aspects of fruit quality formation at the transcriptional regulation level.

Fructose aggravates copper-deficiency-induced non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), is the most common cause of chronic liver disease, affecting 24% of the global population. Accumulating evidence demonstrates that copper deficiency (CuD) is implicated in the development of NAFLD, besides, high fructose consumption by promoting inflammation contributes to NAFLD. However, how CuD and/or fructose (Fru) causes NAFLD is not clearly delineated. The present study aims to investigate the role of CuD and/or fructose supplement on hepatic steatosis and hepatic injury. We established a CuD rat model by feeding weaning male Sprague-Dawley rats for 4 weeks with CuD diet. Fructose was supplemented in drinking water. We found the promoting role of CuD or Fructose (Fru) in the progress of NAFLD, which was aggravated by combination of the two. Furthermore, we presented the alteration of hepatic lipid profiles (including content, composition, and saturation), especially ceramide (Cer), cardiolipin (CL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was closely associated with CuD and/or Fru fed induced-NAFLD in rat models. In conclusion, insufficient copper intake or excessive fructose supplement resulted in adverse effects on the hepatic lipid profile, and fructose supplement causes a further hepatic injury in CuD-induced NAFLD, which illuminated a better understanding of NAFLD.

Fructose Consumption Alters Biogenic Amines Associated with Cardiovascular Disease Risk Factors.

Cardiovascular diseases (CVD) are the major cause of mortality worldwide, whose most prominent risk factor is unhealthy eating habits, such as high fructose intake. Biogenic amines (BAs) perform important functions in the human body. However, the effect of fructose consumption on BA levels is still unclear, as is the association between these and CVD risk factors. This study aimed to establish the association between BA levels and CVD risk factors in animals that consumed fructose. Male Wistar rats received standard chow (n=8) or standard chow + fructose in drinking water (30%) (n=8) over a 24-week period. At the end of this period, the nutritional and metabolic syndrome (MS) parameters and plasmatic BA levels were analyzed. A 5% level of significance was adopted. Fructose consumption led to MS, reduced the levels of tryptophan and 5-hydroxitryptophan, and increased histamine. Tryptophan, histamine, and dopamine showed a correlation with metabolic syndrome parameters. Fructose consumption alters BAs associated with CVD risk factors.

CHREBP/ CHREBP BETA EXPRESSION MEDIATES THE PARADOXICAL EFFECT OF FRUCTOSE ON BODY WEIGHT OF FRUCTOSE-FED RATS BY BROWN ADIPOSE TISSUE ACTIVATION

Objective: Western diet fructose content is a neglected nutrition component, with significant devastating metabolic effects like metabolic syndrome (MeS) and obesity. The data suggest that Food-induced thermogenesis is a contributing factor for regulating body weight. Carbohydrate Responsive Element Binding Protein-beta (ChREBP beta) is recognized now as the regulator of fructose metabolism. Brown adipose tissue (AT) which plays essential role as a thermoregulatory organ, is recognized now also as an endocrine tissue that participates in glucose and lipids metabolism. ChREBP expression is associated with activating of BAT and improve metabolic status. On the other hand, increased ChREBP beta seems to have a deleterious metabolic effect on BAT. Design and method: Sprague-Dawley male rats, 8 weeks old were fed High Fructose Diet (HFRD) or match regular chow for 6 weeks (n = 8). Body weight (BW) and precise food intake were measured weekly. Brown (peri-aortic and interscapular, PA and IS respectively) and white (mesenteric) AT were collected for further molecular studies. Results: HFrD fed rats gain significantly less weight than the control group (from 236±2 to 397±8 vs. 233±2 to 430±9 gr. P&lt;0.05) despite eating an equal food amount (28±1vs.29±1.5 g/rat/week). The expression of uncoupling 1 (UCP1) mRNA, a BAT activation marker, was significantly higher in BAT than in WAT. Fructose consumption increased its BAT expression compared to regular chow. However, the expression of ChREBP and ChREBP beta in BAT was significantly lower in HFrD fed rats. Conclusions: In the HFrD rat model of MeS, fructose consumption leads to lesser weight gain for the same caloric intake. This BW difference is accompanied by the activation of BAT in the HFrD group. This paradoxical effect may be regulated by decreased ChREBP/ChREBP beta expression in response to fructose.

Maternal Intake of Either Fructose or the Artificial Sweetener Acesulfame-K Results in Differential and Sex-Specific Alterations in Markers of Skin Inflammation and Wound Healing Responsiveness in Mouse Offspring: A Pilot Study.

Growing evidence has demonstrated that maternal artificial sweetener (AS) consumption may not be a beneficial alternative when compared to sugar-sweetened beverages and potentially leads to metabolic dysfunction in adult offspring. Compromised skin integrity and wound healing associated with type 2 diabetes can lead to complications such as diabetic pressure injury (PI). In this context, the skin plays an important role in the maintenance of metabolic homeostasis, yet there is limited information on the influence of sugar- or AS-sweetened beverages during pregnancy on developmental programming and offspring skin homeostasis. This study examined the impact of maternal fructose or acesulfame-k consumption on offspring wound healing. Female C57Bl/6 mice received a chow diet ad libitum with either water (CD), fructose (FR; 34.7 mM fructose), or AS (AS; 12.5 mM Acesulfame-K) throughout pregnancy and lactation. PIs were induced in offspring at 9 weeks of age (n = 6/sex/diet). PIs and healthy skin biopsies were collected for later analysis. Maternal AS intake increased skin inflammatory markers in healthy biopsies while an FR diet increased Tgfb expression, and both diets induced subtle changes in inflammatory markers post-wound inducement in a sex-specific manner. Furthermore, a maternal FR diet had a significant effect on pressure wound severity and early wound healing delay, while AS maternal diet had a sex-specific effect on the course of the healing process. This study demonstrates the need for a better understanding of developmental programming as a mediator of later-life skin integrity and wound responsiveness.

Association of fructose consumption with prevalence of functional gastrointestinal disorders manifestations: results from Hellenic National Nutrition and Health Survey (HNNHS).

The study aimed to assess the total prevalence of functional gastrointestinal disorders (FGID), and separately, irritable bowel syndrome (IBS) among adults and to determine their potential association with fructose consumption. Data from the Hellenic National Nutrition and Health Survey were included (3798 adults; 58·9 % females). Information regarding FGID symptomatology was assessed using self-reported physician diagnosis questionnaires the reliability of which were screened using the ROME III, in a sample of the population. Fructose intake was estimated from 24 h recalls, and the MedDiet score was used to assess adherence to the Mediterranean diet. The prevalence of FGID symptomatology was 20·2 %, while 8·2 % had IBS (representing 40·2 % of total FGID). The likelihood of FGID was 28 % higher (95 %CI: 1·03-1·6) and of IBS 49 % (95 %CI: 1·08-2·05) in individuals with higher fructose intake than with lower intake (3rd tertile compared with 1st). When area of residence was accounted for, individuals residing in the Greek islands had a significantly lower probability of FGID and IBS compared with those residing in Mainland and the main Metropolitan areas, with Islanders also achieving a higher MedDiet score and lower added sugar intake, comparatively to inhabitants of the main metropolitan areas. FGID and IBS symptomatology was most prominent among individuals with higher fructose consumption, and this was most conspicuous in areas with a lower Mediterranean diet adherence, suggesting that the dietary source of fructose rather than total fructose should be examined in relation to FGID.