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Obesity and Metabolic Syndrome in Kidney Transplantation: The Role of Dietary Fructose and Systemic Endotoxemia.
Chan, W, Smith, B, Stegall, M, Borrows, R
Transplantation. 2019;(1):191-201
Abstract
BACKGROUND The concepts that obesity is merely a consequence of overeating, and that metabolic health then reflects obesity, may be insufficient and potentially flawed. The role of fructose intake and metabolic endotoxemia has gained attention recently, but data in kidney transplantation are lacking. This study evaluated the risk factors for metabolic syndrome (MS), its components, and other associated markers in kidney transplant recipients (KTRs), focusing particularly on fructose intake and systemic endotoxemia. METHODS This cross-sectional observational study enrolled 128 KTRs longer than 1 year posttransplantation. Clinical, biochemical, anthropometric, and questionnaire assessments were undertaken. RESULTS Obesity (body mass index, ≥30 kg/m) and MS (International Diabetes Federation Definition) were found in 36.7% and 50% of KTRs, respectively. Both increased fructose intake (P = 0.01) and endotoxin level (P = 0.02) were independently associated with MS; and higher fructose intake was independently associated with obesity (P < 0.001). Specifically, increased fructose intake was associated with the central obesity (P = 0.01) and hyperglycemia (P < 0.001) criteria of MS, whereas higher endotoxin level was associated with the hypertriglyceridemia (P = 0.003) and low HDL cholesterol concentration (P = 0.002) criteria of MS. Neither saturated fat nor total caloric intakes were independently associated with obesity and MS; and neither obesity nor central obesity were independently associated with the dyslipidemia and hyperglycemia criteria of MS. Principal component analysis demonstrated relationships between higher levels of endotoxin, soluble endothelial selectin, triglycerides, and insulin resistance (r > 0.6), as well as relationships between increased fructose intake, inflammation, and blood glucose (r > 0.6). CONCLUSIONS Dietary modifications through decreasing fructose intake and addressing systemic endotoxemia are plausible targets for improving metabolic health of KTRs.
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Fructose co-ingestion to increase carbohydrate availability in athletes.
Fuchs, CJ, Gonzalez, JT, van Loon, LJC
The Journal of physiology. 2019;(14):3549-3560
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Abstract
Carbohydrate availability is important to maximize endurance performance during prolonged bouts of moderate- to high-intensity exercise as well as for acute post-exercise recovery. The primary form of carbohydrates that are typically ingested during and after exercise are glucose (polymers). However, intestinal glucose absorption can be limited by the capacity of the intestinal glucose transport system (SGLT1). Intestinal fructose uptake is not regulated by the same transport system, as it largely depends on GLUT5 as opposed to SGLT1 transporters. Combining the intake of glucose plus fructose can further increase total exogenous carbohydrate availability and, as such, allow higher exogenous carbohydrate oxidation rates. Ingesting a mixture of both glucose and fructose can improve endurance exercise performance compared to equivalent amounts of glucose (polymers) only. Fructose co-ingestion can also accelerate post-exercise (liver) glycogen repletion rates, which may be relevant when rapid (<24 h) recovery is required. Furthermore, fructose co-ingestion can lower gastrointestinal distress when relatively large amounts of carbohydrate (>1.2 g/kg/h) are ingested during post-exercise recovery. In conclusion, combined ingestion of fructose with glucose may be preferred over the ingestion of glucose (polymers) only to help trained athletes maximize endurance performance during prolonged moderate- to high-intensity exercise sessions and accelerate post-exercise (liver) glycogen repletion.
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Bioelectrocatalytic performance of d-fructose dehydrogenase.
Adachi, T, Kaida, Y, Kitazumi, Y, Shirai, O, Kano, K
Bioelectrochemistry (Amsterdam, Netherlands). 2019;:1-9
Abstract
This review summarizes the bioelectrocatalytic properties of d-fructose dehydrogenase (FDH), while taking into consideration its enzymatic characteristics. FDH is a membrane-bound flavohemo-protein with a molecular mass of 138 kDa, and it catalyzes the oxidation of d-fructose to 5-keto-d-fructose. The characteristic feature of FDH is its strong direct-electron-transfer (DET)-type bioelectrocatalytic activity. The pathway of the DET-type reaction is discussed. An overview of the application of FDH-based bioelectrocatalysis to biosensors and biofuel cells is also presented, and the benefits and problems associated with it are extensively discussed.
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A prospective randomized, double-blind, placebo-controlled, dose-response relationship study to investigate efficacy of fructo-oligosaccharides (FOS) on human gut microflora.
Tandon, D, Haque, MM, Gote, M, Jain, M, Bhaduri, A, Dubey, AK, Mande, SS
Scientific reports. 2019;(1):5473
Abstract
Fructo-oligosaccharides (FOS), a prebiotic supplement, is known for its Bifidogenic capabilities. However, aspects such as effect of variable quantities of FOS intake on gut microbiota, and temporal dynamics of gut microbiota (transitioning through basal, dosage, and follow-up phases) has not been studied in detail. This study investigated these aspects through a randomized, double-blind, placebo-controlled, dose-response relationship study. The study involved 80 participants being administered FOS at three dose levels (2.5, 5, and 10 g/day) or placebo (Maltodextrin 10 g/day) during dosage phase. Microbial DNA extracted from fecal samples collected at 9 intervening time-points was sequenced and analysed. Results indicate that FOS consumption increased the relative abundance of OTUs belonging to Bifidobacterium and Lactobacillus. Interestingly, higher FOS dosage appears to promote, in contrast to Maltodextrin, the selective proliferation of OTUs belonging to Lactobacillus. While consumption of prebiotics increased bacterial diversity, withdrawal led to its reduction. Apart from probiotic bacteria, a significant change was also observed in certain butyrate-producing microbes like Faecalibacterium, Ruminococcus and Oscillospira. The positive impact of FOS on butyrate-producing bacteria and FOS-mediated increased bacterial diversity reinforces the role of prebiotics in conferring beneficial functions to the host.
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Fructose Consumption Contributes to Hyperinsulinemia in Adolescents With Obesity Through a GLP-1-Mediated Mechanism.
Galderisi, A, Giannini, C, Van Name, M, Caprio, S
The Journal of clinical endocrinology and metabolism. 2019;(8):3481-3490
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CONTEXT The consumption of high-fructose beverages is associated with a higher risk for obesity and diabetes. Fructose can stimulate glucagon-like peptide 1 (GLP-1) secretion in lean adults, in the absence of any anorexic effect. OBJECTIVE We hypothesized that the ingestion of glucose and fructose may differentially stimulate GLP-1 and insulin response in lean adolescents and adolescents with obesity. DESIGN We studied 14 lean adolescents [four females; 15.9 ± 1.6 years of age; body mass index (BMI), 21.8 ± 2.2 kg/m2] and 23 adolescents with obesity (five females; 15.1 ± 1.6 years of age; BMI, 34.5 ± 4.6 kg/m2). Participants underwent a baseline oral glucose tolerance test to determine their glucose tolerance and estimate insulin sensitivity and β-cell function [oral disposition index (oDIcpep)]. Eligible subjects received, in a double-blind, crossover design, 75 g of glucose or fructose. Plasma was obtained every 10 minutes for 60 minutes for the measures of glucose, insulin, and GLP-1 (radioimmunoassay) and glucose-dependent insulinotropic polypeptide (GIP; ELISA). Incremental glucose and hormone levels were compared between lean individuals and those with obesity by a linear mixed model. The relationship between GLP-1 increment and oDIcpep was evaluated by regression analysis. RESULTS Following the fructose challenge, plasma glucose excursions were similar in both groups, yet the adolescents with obesity exhibited a greater insulin (P < 0.001) and GLP-1 (P < 0.001) increase than did their lean peers. Changes in GIP were similar in both groups. After glucose ingestion, the GLP-1 response (P < 0.001) was higher in the lean group. The GLP-1 increment during 60 minutes from fructose drink was correlated with a lower oDIcpep (r2 = 0.22, P = 0.009). CONCLUSION Fructose, but not glucose, ingestion elicits a higher GLP-1 and insulin response in adolescents with obesity than in lean adolescents. Fructose consumption may contribute to the hyperinsulinemic phenotype of adolescent obesity through a GLP-1-mediated mechanism.
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Differential capability of metabolic substrates to promote hepatocellular lipid accumulation.
Hoang, NA, Richter, F, Schubert, M, Lorkowski, S, Klotz, LO, Steinbrenner, H
European journal of nutrition. 2019;(8):3023-3034
Abstract
PURPOSE Excessive storage of triacylglycerides (TAGs) in lipid droplets within hepatocytes is a hallmark of non-alcoholic fatty liver disease (NAFLD), one of the most widespread metabolic disorders in Western societies. For the purpose of exploring molecular pathways in NAFLD development and testing potential drug candidates, well-characterised experimental models of ectopic TAG storage in hepatocytes are needed. METHODS Using an optimised Oil Red O assay, immunoblotting and real-time qRT-PCR, we compared the capability of dietary monosaccharides and fatty acids to promote lipid accumulation in HepG2 human hepatoma cells. RESULTS Both high glucose and high fructose resulted in intracellular lipid accumulation after 48 h, and this was further augmented (up to twofold, as compared to basal levels) by co-treatment with the lipogenesis-stimulating hormone insulin and the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-α), respectively. The fatty acids palmitic and oleic acid were even more effective than these carbohydrates, inducing significantly elevated TAG storage already after 24 h of treatment. Highest (about threefold) increases in lipid accumulation were observed upon treatment with oleic acid, alone as well as in combinations with palmitic acid or with high glucose and insulin. Increases in protein levels of a major lipid droplet coat protein, perilipin-2 (PLIN2), mirrored intracellular lipid accumulation following different treatment regimens. CONCLUSIONS Several treatment regimens of excessive fat and sugar supply promoted lipid accumulation in HepG2 cells, albeit with differences in the extent and rapidity of steatogenesis. PLIN2 is a candidate molecular marker of sustained lipid accumulation in HepG2 cells.
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Short-Term Isocaloric Intake of a Fructose- but not Glucose-Rich Diet Affects Bacterial Endotoxin Concentrations and Markers of Metabolic Health in Normal Weight Healthy Subjects.
Nier, A, Brandt, A, Rajcic, D, Bruns, T, Bergheim, I
Molecular nutrition & food research. 2019;(6):e1800868
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SCOPE Dietary pattern and impairments of intestinal barrier function are discussed to be critical in the development of metabolic impairments. Here, it is determined if an isocaloric exchange of complex carbohydrates with monosaccharides affects markers of intestinal permeability and metabolic health in healthy subjects. METHODS AND RESULTS After a dietary standardization for 4 days, all 12 subjects aged 21-33 years receive an isocaloric fructose- and glucose-enriched diet for 3 days separated by a wash-out phase. Anthropometry, blood pressure, markers of intestinal permeability and metabolic as well as inflammatory parameters are determined in blood samples or isolated peripheral blood mononuclear cells collected at baseline, after standardizations and the monosaccharide interventions, respectively. While anthropometric and inflammatory parameters are not changed, the intake of an isocaloric fructose- but not glucose-enriched diet is associated with a significant increase of bacterial endotoxin plasma levels and alanine aminotransferase activity in serum, while total plasma nitrate/nitrite concentrations are significantly decreased. In peripheral blood mononuclear cells, Toll like receptors 4, 2, and MYD88 mRNA expressions are significantly induced after the fructose-rich but not the glucose-rich diet. CONCLUSION In metabolically healthy subjects, even a short-term intake of a fructose-rich diet can elevate bacterial endotoxin levels and change markers of liver health and vascular endothelial function.
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High fructose consumption with a high-protein meal is associated with decreased glycemia and increased thermogenesis but reduced fat oxidation: A randomized controlled trial.
Camps, SG, Koh, HR, Wang, NX, Henry, CJ
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:77-82
Abstract
OBJECTIVES Fructose is often recommended due to its ability to lower glycemic response and its increased thermogenic effect. Additionally, proteins can reduce the glycemic response of carbohydrate-rich foods and have a high diet-induced thermogenesis (DIT). The aim of this study was to investigate whether the inclusion of fructose in a high-protein meal would demonstrate metabolic advantages. METHODS Nineteen Asian women (body mass index 17-28 kg/m2) consumed a low-glycemic index (GI; fructose) or high GI (glucose), high-protein breakfast followed by a standardized lunch in a randomized crossover design. Simultaneously, 8-h continuous glucose monitoring provided incremental area under the curve (iAUC) and 4-h indirect calorimetry provided DIT and respiratory quotient (RQ). RESULTS The low GI diet resulted in a lower glucose iAUC (135 ± 25 versus 212 ± 23 mmol/L, P < 0.05) following breakfast, but no second-meal effect after the standardized lunch (217 ± 37 versus 228 ± 27 mmol/L, P < 0.05) compared with the high GI diet. Furthermore, 4-h DIT was greater (40.6 ± 2.3 versus 34.9 ± 1.8 kcal, P < 0.05) and RQ was increased after the fructose high-protein breakfast (0.047 ± 0.009 versus 0.028 ± 0.009, P < 0.05) compared with the glucose meal. CONCLUSIONS Fructose is an effective sweetener in reducing glycemia and increasing DIT in the presence of a high-protein diet. However, the reduced fat oxidation after high fructose consumption might present a risk for increased lipogenesis.
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Different acute effects of fructose and glucose administration on hepatic fat content.
Dusilová, T, Kovář, J, Drobný, M, Šedivý, P, Dezortová, M, Poledne, R, Zemánková, K, Hájek, M
The American journal of clinical nutrition. 2019;(6):1519-1526
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BACKGROUND Diets rich in fat and added sugars (especially fructose) play an important role in the pathogenesis of nonalcoholic liver disease (NAFLD), but there is only limited information on the acute effects of these nutrients on hepatic fat content (HFC). OBJECTIVES We therefore explored how the administration of high-fat load, glucose, fructose, and combinations thereof affects HFC measured in vivo using proton magnetic resonance spectroscopy (1H-MRS) in healthy subjects. METHODS Ten healthy nonsteatotic male volunteers (age 38.5 ± 9.6 y, body mass index [BMI, kg/m2] 26.9 ± 2.7) underwent, in random order, 6 experiments, each lasting 8 h, that included: 1) fasting; 2) a high-fat load (150 g of fat [dairy cream] at time 0); 3) glucose (3 doses of 50 g at 0, 2, and 4 h); 4) a high-fat load with glucose; 5) fructose (3 doses of 50 g at 0, 2, and 4 h); and 6) a high-fat load with fructose. HFC was measured using 1H-MRS prior to test meal administration (before time 0) and at 3 and 6 h. Plasma concentrations of triglycerides, nonesterified fatty acids, glucose, and insulin were monitored throughout each experiment. RESULTS HFC increased to 119 ± 19% (P < 0.05) and 117 ± 17% (P < 0.01) of baseline when subjects consumed a high-fat load alone or a high-fat load with fructose, respectively, but was not affected when glucose was coadministered with a high-fat load. HFC was not affected when subjects had fasted or had consumed repeated doses of fructose. When subjects were administered 3 doses of glucose, HFC dropped to 85 ± 13% (P < 0.05) of baseline. CONCLUSIONS Our results demonstrate that fructose and glucose have a different immediate impact on HFC in humans in vivo. Clinical trial registry: The study was registered at clinicaltrials.gov and obtained clinicaltrials.gov identifier: NCT03680248.
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Fructose malabsorption in asymptomatic children and in patients with functional chronic abdominal pain: a prospective comparative study.
Martínez-Azcona, O, Moreno-Álvarez, A, Seoane-Pillado, T, Niño-Grueiro, I, Ramiro-Comesaña, A, Menéndez-Riera, M, Pérez-Domínguez, M, Solar-Boga, A, Leis-Trabazo, R
European journal of pediatrics. 2019;(9):1395-1403
Abstract
The objective of this prospective cohort study was to compare fructose malabsorption in patients with functional chronic abdominal pain and in healthy children. The sample was divided into two groups: asymptomatic children and pain-predominant functional gastrointestinal disorders according to the Rome IV criteria. All children were tested for fructose malabsorption by a standardized breath hydrogen test. Hydrogen and methane were measured and the test was presumed positive when it exceeded 20 ppm above baseline. If positive, patients were given a low-fructose diet and the response was evaluated. One hundred five children were included (34 healthy children, 71 with functional chronic abdominal pain), with similar demographic characteristics in both groups (35.2% male, age 9.5 ± 2.8 years). Hydrogen levels in breath were tested through a hydrogen test for fructose demonstrating malabsorption in 58.8% of healthy children (95%CI 40.8%-76.8%) and in 40.8% of children with chronic abdominal pain (95%CI 28.7%-53.0%), removing those who had bacterial overgrowth. Twenty-one of 31 patients with symptoms and a positive test (72.4%) reported an improvement on a low-fructose diet.Conclusion: Fructose malabsorption is more common in asymptomatic children than in patients with chronic abdominal pain. Better standardized test conditions are necessary to improve accuracy of diagnosis before using this test in clinical practice. What is Known: • Although fructose malabsorption is believed to be related with chronic abdominal pain, high-quality evidence is lacking. • Concerns have raised regarding the use of breath hydrogen test for fructose malabsorption in children with chronic abdominal pain. What is New: • Fructose malabsorption is not more common in children with pain-predominant functional gastrointestinal disorders than in asymptomatic children. • Improvement in symptoms with low-fructose diet may indicate that, although patients with pain-predominant functional gastrointestinal disorders did not have a higher percentage of malabsorption, they had greater fructose intolerance.