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Carbohydrate Metabolism in Health and Disease

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (30 November 2017) | Viewed by 243690

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Guest Editor
Department for Health, University of Bath, Bath BA2 7AY, UK
Interests: Interactions between nutrition and physical activity in the context of health and disease, with a particular focus on the manipulation of carbohydrate and fat metabolism to maintain health and improve sports performance

Special Issue Information

Dear Colleagues,

Carbohydrate metabolism is a key aspect of health and optimal function in a variety of species, including humans. A primary alteration in major global diseases, such as cardiovascular disease and diabetes, is dysregulation of carbohydrate metabolism. Furthermore, certain disease outcomes may be impacted by the amount and type dietary carbohydrates consumed. Finally, carbohydrate availability is essential for optimal performance in many sporting events. We welcome the submission of manuscripts, either describing original research, or reviewing scientific literature on the topic of carbohydrate metabolism in health and disease.

Dr. Javier T. Gonzalez
Guest Editor

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Keywords

  • Carbohydrates
  • Metabolic syndrome
  • Glucose
  • Exercise
  • Sports Nutrition
  • Sugars
  • Fructose
  • Insulin

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Published Papers (17 papers)

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Research

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15 pages, 4398 KiB  
Article
ChREBP-Knockout Mice Show Sucrose Intolerance and Fructose Malabsorption
by Takehiro Kato, Katsumi Iizuka, Ken Takao, Yukio Horikawa, Tadahiro Kitamura and Jun Takeda
Nutrients 2018, 10(3), 340; https://doi.org/10.3390/nu10030340 - 12 Mar 2018
Cited by 33 | Viewed by 7566
Abstract
We have previously reported that 60% sucrose diet-fed ChREBP knockout mice (KO) showed body weight loss resulting in lethality. We aimed to elucidate whether sucrose and fructose metabolism are impaired in KO. Wild-type mice (WT) and KO were fed a diet containing 30% [...] Read more.
We have previously reported that 60% sucrose diet-fed ChREBP knockout mice (KO) showed body weight loss resulting in lethality. We aimed to elucidate whether sucrose and fructose metabolism are impaired in KO. Wild-type mice (WT) and KO were fed a diet containing 30% sucrose with/without 0.08% miglitol, an α-glucosidase inhibitor, and these effects on phenotypes were tested. Furthermore, we compared metabolic changes of oral and peritoneal fructose injection. A thirty percent sucrose diet feeding did not affect phenotypes in KO. However, miglitol induced lethality in 30% sucrose-fed KO. Thirty percent sucrose plus miglitol diet-fed KO showed increased cecal contents, increased fecal lactate contents, increased growth of lactobacillales and Bifidobacterium and decreased growth of clostridium cluster XIVa. ChREBP gene deletion suppressed the mRNA levels of sucrose and fructose related genes. Next, oral fructose injection did not affect plasma glucose levels and liver fructose contents; however, intestinal sucrose and fructose related mRNA levels were increased only in WT. In contrast, peritoneal fructose injection increased plasma glucose levels in both mice; however, the hepatic fructose content in KO was much higher owing to decreased hepatic Khk mRNA expression. Taken together, KO showed sucrose intolerance and fructose malabsorption owing to decreased gene expression. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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13 pages, 893 KiB  
Article
Chronic Ketogenic Low Carbohydrate High Fat Diet Has Minimal Effects on Acid–Base Status in Elite Athletes
by Amelia J. Carr, Avish P. Sharma, Megan L. Ross, Marijke Welvaert, Gary J. Slater and Louise M. Burke
Nutrients 2018, 10(2), 236; https://doi.org/10.3390/nu10020236 - 18 Feb 2018
Cited by 22 | Viewed by 24893
Abstract
Although short (up to 3 days) exposure to major shifts in macronutrient intake appears to alter acid–base status, the effects of sustained (>1 week) interventions in elite athletes has not been determined. Using a non-randomized, parallel design, we examined the effect of adaptations [...] Read more.
Although short (up to 3 days) exposure to major shifts in macronutrient intake appears to alter acid–base status, the effects of sustained (>1 week) interventions in elite athletes has not been determined. Using a non-randomized, parallel design, we examined the effect of adaptations to 21 days of a ketogenic low carbohydrate high fat (LCHF) or periodized carbohydrate (PCHO) diet on pre- and post-exercise blood pH, and concentrations of bicarbonate [HCO3] and lactate [La] in comparison to a high carbohydrate (HCHO) control. Twenty-four (17 male and 7 female) elite-level race walkers completed 21 days of either LCHF (n = 9), PCHO (n = 7), or HCHO (n = 8) under controlled diet and training conditions. At baseline and post-intervention, blood pH, blood [HCO3], and blood [La] were measured before and after a graded exercise test. Net endogenous acid production (NEAP) over the previous 48–72 h was also calculated from monitored dietary intake. LCHF was not associated with significant differences in blood pH, [HCO3], or [La], compared with the HCHO diet pre- or post-exercise, despite a significantly higher NEAP (mEq·day−1) (95% CI = (10.44; 36.04)). Our results indicate that chronic dietary interventions are unlikely to influence acid–base status in elite athletes, which may be due to pre-existing training adaptations, such as an enhanced buffering capacity, or the actions of respiratory and renal pathways, which have a greater influence on regulation of acid–base status than nutritional intake. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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11 pages, 2081 KiB  
Article
The Influence of Pre-Exercise Glucose versus Fructose Ingestion on Subsequent Postprandial Lipemia
by Tsung-Jen Yang, Chih-Hui Chiu, Mei-Hui Tseng, Cheng-Kang Chang and Ching-Lin Wu
Nutrients 2018, 10(2), 149; https://doi.org/10.3390/nu10020149 - 29 Jan 2018
Cited by 3 | Viewed by 6280
Abstract
Ingestion of low glycemic index (LGI) carbohydrate (CHO) before exercise induced less insulin response and higher fat oxidation than that of high GI (HGI) CHO during subsequent exercise. However, the effect on the subsequent postprandial lipid profile is still unclear. Therefore, the aim [...] Read more.
Ingestion of low glycemic index (LGI) carbohydrate (CHO) before exercise induced less insulin response and higher fat oxidation than that of high GI (HGI) CHO during subsequent exercise. However, the effect on the subsequent postprandial lipid profile is still unclear. Therefore, the aim of this study was to investigate ingestion of CHO drinks with different GI using fructose and glucose before endurance exercise on the subsequent postprandial lipid profile. Eight healthy active males completed two experimental trials in randomized double-blind cross-over design. All participants ingested 500 mL CHO (75 g) solution either fructose (F) or glucose (G) before running on the treadmill at 60% VO2max for 1 h. Participants were asked to take an oral fat tolerance test (OFTT) immediately after the exercise. Blood samples were obtained for plasma and serum analysis. The F trial was significantly lower than the G trial in TG total area under the curve (AUC; 9.97 ± 3.64 vs. 10.91 ± 3.56 mmol × 6 h/L; p = 0.033) and incremental AUC (6.57 ± 2.46 vs. 7.14 ± 2.64 mmol/L × 6 h, p = 0.004). The current data suggested that a pre-exercise fructose drink showed a lower postprandial lipemia than a glucose drink after the subsequent high-fat meal. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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12 pages, 1259 KiB  
Article
Type-4 Resistant Starch in Substitution for Available Carbohydrate Reduces Postprandial Glycemic Response and Hunger in Acute, Randomized, Double-Blind, Controlled Study
by Maria L. Stewart, Meredith L. Wilcox, Marjorie Bell, Mary A. Buggia and Kevin C. Maki
Nutrients 2018, 10(2), 129; https://doi.org/10.3390/nu10020129 - 26 Jan 2018
Cited by 50 | Viewed by 8977
Abstract
Resistant starch (RS) is a type of dietary fiber that has been acknowledged for multiple physiological benefits. Resistant starch type 4 (RS4) is a subcategory of RS that has been more intensively studied as new types of RS4 emerge in the food supply. [...] Read more.
Resistant starch (RS) is a type of dietary fiber that has been acknowledged for multiple physiological benefits. Resistant starch type 4 (RS4) is a subcategory of RS that has been more intensively studied as new types of RS4 emerge in the food supply. The primary aim of this randomized, double-blind, controlled study was to characterize the postprandial glucose response in healthy adults after consuming a high fiber scone containing a novel RS4 or a low fiber control scone without RS4. Secondary aims included assessment of postprandial insulin response, postprandial satiety, and gastrointestinal tolerance. The fiber scone significantly reduced postprandial glucose and insulin incremental areas under the curves (43–45% reduction, 35–40% reduction, respectively) and postprandial glucose and insulin maximum concentrations (8–10% and 22% reduction, respectively). The fiber scone significantly reduced hunger and desire to eat during the 180 min following consumption and yielded no gastrointestinal side effects compared with the control scone. The results from this study demonstrate that a ready-to-eat baked-good, such as a scone, can be formulated with RS4 replacing refined wheat flour to yield statistically significant and clinically meaningful reductions in blood glucose and insulin excursions. This is the first study to report increased satiety after short-term RS4 intake, which warrants further investigation in long-term feeding studies. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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11 pages, 1222 KiB  
Article
Post-Exercise Carbohydrate-Energy Replacement Attenuates Insulin Sensitivity and Glucose Tolerance the Following Morning in Healthy Adults
by Harry L. Taylor, Ching-Lin Wu, Yung-Chih Chen, Pin-Ging Wang, Javier T. Gonzalez and James A. Betts
Nutrients 2018, 10(2), 123; https://doi.org/10.3390/nu10020123 - 25 Jan 2018
Cited by 17 | Viewed by 22606
Abstract
The carbohydrate deficit induced by exercise is thought to play a key role in increased post-exercise insulin action. However, the effects of replacing carbohydrate utilized during exercise on postprandial glycaemia and insulin sensitivity are yet to be determined. This study therefore isolated the [...] Read more.
The carbohydrate deficit induced by exercise is thought to play a key role in increased post-exercise insulin action. However, the effects of replacing carbohydrate utilized during exercise on postprandial glycaemia and insulin sensitivity are yet to be determined. This study therefore isolated the extent to which the insulin-sensitizing effects of exercise are dependent on the carbohydrate deficit induced by exercise, relative to other exercise-mediated mechanisms. Fourteen healthy adults performed a 90-min run at 70% V ˙ O 2 max starting at 1600–1700 h before ingesting either a non-caloric artificially-sweetened placebo solution (CHO-DEFICIT) or a 15% carbohydrate solution (CHO-REPLACE; 221.4 ± 59.3 g maltodextrin) to precisely replace the measured quantity of carbohydrate oxidized during exercise. The alternate treatment was then applied one week later in a randomized, placebo-controlled, and double-blinded crossover design. A standardized low-carbohydrate evening meal was consumed in both trials before overnight recovery ahead of a two-hour oral glucose tolerance test (OGTT) the following morning to assess glycemic and insulinemic responses to feeding. Compared to the CHO-DEFICIT condition, CHO-REPLACE increased the incremental area under the plasma glucose curve by a mean difference of 68 mmol·L−1 (95% CI: 4 to 132 mmol·L−1; p = 0.040) and decreased the Matsuda insulin sensitivity index by a mean difference of −2 au (95% CI: −1 to −3 au; p = 0.001). This is the first study to demonstrate that post-exercise feeding to replaceme the carbohydrate expended during exercise can attenuate glucose tolerance and insulin sensitivity the following morning. The mechanism through which exercise improves insulin sensitivity is therefore (at least in part) dependent on carbohydrate availability and so the day-to-day metabolic health benefits of exercise might be best attained by maintaining a carbohydrate deficit overnight. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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17 pages, 3454 KiB  
Article
Amaranthus caudatus Stimulates Insulin Secretion in Goto-Kakizaki Rats, a Model of Diabetes Mellitus Type 2
by Silvia Zambrana, Lena C. E. Lundqvist, Virginia Veliz, Sergiu-Bogdan Catrina, Eduardo Gonzales and Claes-Göran Östenson
Nutrients 2018, 10(1), 94; https://doi.org/10.3390/nu10010094 - 15 Jan 2018
Cited by 20 | Viewed by 7024
Abstract
Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a pseudo-cereal with reported anti-diabetic effects that is usually consumed in food preparations in Bolivia. This study evaluated the anti-diabetic [...] Read more.
Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a pseudo-cereal with reported anti-diabetic effects that is usually consumed in food preparations in Bolivia. This study evaluated the anti-diabetic nutraceutical property of an AC hydroethanolic extract that contains mainly sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)), in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats. A single oral administration of AC extract (2000 mg/kg body weight) improved glucose tolerance during Oral Glucose Tolerance Tests (OGTT) in both GK rats and in W rats. Long-term treatment (21 days) with AC (1000 mg/kg b.w.) improved the glucose tolerance evaluated by the area under the curve (AUC) of glucose levels during the OGTT, in both GK and W rats. The HbA1c levels were reduced in both GK (19.83%) and W rats (10.7%). This effect was secondary to an increase in serum insulin levels in both GK and W rats and confirmed in pancreatic islets, isolated from treated animals, where the chronic AC exposure increased the insulin production 4.1-fold in GK and 3.7-fold in W rat islets. Furthermore, the effect of AC on in vitro glucose-dependent insulin secretion (16.7 mM glucose) was concentration-dependent up to 50 mg/mL, with 8.5-fold increase in GK and 5.7-fold in W rat islets, and the insulin secretion in perifused GK and W rat islets increased 31 and nine times, respectively. The mechanism of action of AC on insulin secretion was shown to involve calcium, PKA and PKC activation, and G-protein coupled-exocytosis since the AC effect was reduced 38% by nifedipine (L-type channel inhibitor), 77% by H89 (PKA inhibitor), 79% by Calphostine-C (PKC inhibitor) and 20% by pertussis toxin (G-protein suppressor). Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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20 pages, 1212 KiB  
Article
Metabolic Responses to Carbohydrate Ingestion during Exercise: Associations between Carbohydrate Dose and Endurance Performance
by Michael L. Newell, Gareth A. Wallis, Angus M. Hunter, Kevin D. Tipton and Stuart D. R. Galloway
Nutrients 2018, 10(1), 37; https://doi.org/10.3390/nu10010037 - 3 Jan 2018
Cited by 25 | Viewed by 16525
Abstract
Carbohydrate (CHO) ingestion during exercise lasting less than three hours improves endurance exercise performance but there is still debate about the optimal dose. We utilised stable isotopes and blood metabolite profiles to further examine metabolic responses to CHO (glucose only) ingestion in the [...] Read more.
Carbohydrate (CHO) ingestion during exercise lasting less than three hours improves endurance exercise performance but there is still debate about the optimal dose. We utilised stable isotopes and blood metabolite profiles to further examine metabolic responses to CHO (glucose only) ingestion in the 20–64 g·h−1 range, and to determine the association with performance outcome. In a double-blind, randomized cross-over design, male cyclists (n = 20, mean ± SD, age 34 ± 10 years, mass 75.8 ± 9 kg, peak power output 394 ± 36 W, VO2max 62 ± 9 mL·kg−1·min−1) completed four main experimental trials. Each trial involved a two-hour constant load ride (185 ± 25 W) followed by a time trial, where one of three CHO beverages, or a control (water), were administered every 15 min, providing 0, 20, 39 or 64 g CHO·h−1. Dual glucose tracer techniques, indirect calorimetry and blood analyses were used to determine glucose kinetics, exogenous CHO oxidation (EXO), endogenous CHO and fat oxidation; and metabolite responses. Regression analysis revealed that total exogenous CHO oxidised in the second hour of exercise, and suppression of serum NEFA concentration provided the best prediction model of performance outcome. However, the model could only explain ~19% of the variance in performance outcome. The present data demonstrate that consuming ~40 g·h−1 of CHO appears to be the minimum ingestion rate required to induce metabolic effects that are sufficient to impact upon performance outcome. These data highlight a lack of performance benefit and few changes in metabolic outcomes beyond an ingestion rate of 39 g·h−1. Further work is required to explore dose-response effects of CHO feeding and associations between multiple metabolic parameters and subsequent performance outcome. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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1034 KiB  
Article
Prebiotic Dietary Fiber and Gut Health: Comparing the in Vitro Fermentations of Beta-Glucan, Inulin and Xylooligosaccharide
by Justin L. Carlson, Jennifer M. Erickson, Julie M. Hess, Trevor J. Gould and Joanne L. Slavin
Nutrients 2017, 9(12), 1361; https://doi.org/10.3390/nu9121361 - 15 Dec 2017
Cited by 173 | Viewed by 17480
Abstract
Prebiotic dietary fiber supplements are commonly consumed to help meet fiber recommendations and improve gastrointestinal health by stimulating beneficial bacteria and the production of short-chain fatty acids (SCFAs), molecules beneficial to host health. The objective of this research project was to compare potential [...] Read more.
Prebiotic dietary fiber supplements are commonly consumed to help meet fiber recommendations and improve gastrointestinal health by stimulating beneficial bacteria and the production of short-chain fatty acids (SCFAs), molecules beneficial to host health. The objective of this research project was to compare potential prebiotic effects and fermentability of five commonly consumed fibers using an in vitro fermentation system measuring changes in fecal microbiota, total gas production and formation of common SCFAs. Fecal donations were collected from three healthy volunteers. Materials analyzed included: pure beta-glucan, Oatwell (commercially available oat-bran containing 22% oat β-glucan), xylooligosaccharides (XOS), WholeFiber (dried chicory root containing inulin, pectin, and hemi/celluloses), and pure inulin. Oatwell had the highest production of propionate at 12 h (4.76 μmol/mL) compared to inulin, WholeFiber and XOS samples (p < 0.03). Oatwell’s effect was similar to those of the pure beta-glucan samples, both samples promoted the highest mean propionate production at 24 h. XOS resulted in a significant increase in the genus Bifidobacterium after 24 h of fermentation (0 h:0.67 OTUs (operational taxonomic unit); 24 h:5.22 OTUs; p = 0.038). Inulin and WholeFiber increased the beneficial genus Collinsella, consistent with findings in clinical studies. All analyzed compounds were fermentable and promoted the formation of beneficial SCFAs. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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1332 KiB  
Article
Slowly Digestible Carbohydrate for Balanced Energy: In Vitro and In Vivo Evidence
by Vishnupriya Gourineni, Maria L. Stewart, Rob Skorge and Bernard C. Sekula
Nutrients 2017, 9(11), 1230; https://doi.org/10.3390/nu9111230 - 10 Nov 2017
Cited by 26 | Viewed by 7952
Abstract
There is growing interest among consumers in foods for sustained energy management, and an increasing number of ingredients are emerging to address this demand. The SUSTRA™ 2434 slowly digestible carbohydrate is a blend of tapioca flour and corn starch, with the potential to [...] Read more.
There is growing interest among consumers in foods for sustained energy management, and an increasing number of ingredients are emerging to address this demand. The SUSTRA™ 2434 slowly digestible carbohydrate is a blend of tapioca flour and corn starch, with the potential to provide balanced energy after a meal. The aim of the study was to characterize this starch’s digestion profile in vitro (modified Englyst assay) and in vivo (intact and cecectomized rooster study), and to determine its effects on available energy, by measuring post-prandial glycemia in healthy adults (n = 14), in a randomized, double-blind, placebo-controlled, cross-over study, with two food forms: cold-pressed bar and pudding. The in vitro starch digestion yielded a high slowly digestible fraction (51%) compared to maltodextrin (9%). In the rooster digestibility model, the starch was highly digestible (94%). Consumption of slowly digestible starch (SDS), in an instant pudding or bar, yielded a significantly lower glycemic index compared to a control. At individual time points, the SDS bar and pudding yielded blood glucose levels with significantly lower values at 30–60 min and significantly higher values at 120–240 min, demonstrating a balanced energy release. This is the first study to comprehensively characterize the physiological responses to slowly digestible starch (tapioca and corn blend) in in vitro and in vivo studies. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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1308 KiB  
Article
Kiwifruit Non-Sugar Components Reduce Glycaemic Response to Co-Ingested Cereal in Humans
by Suman Mishra, Haley Edwards, Duncan Hedderley, John Podd and John Monro
Nutrients 2017, 9(11), 1195; https://doi.org/10.3390/nu9111195 - 30 Oct 2017
Cited by 19 | Viewed by 6404
Abstract
Kiwifruit (KF) effects on the human glycaemic response to co-ingested wheat cereal were determined. Participants (n = 20) consumed four meals in random order, all being made to 40 g of the same available carbohydrate, by adding kiwifruit sugars (KF sug; glucose, fructose, [...] Read more.
Kiwifruit (KF) effects on the human glycaemic response to co-ingested wheat cereal were determined. Participants (n = 20) consumed four meals in random order, all being made to 40 g of the same available carbohydrate, by adding kiwifruit sugars (KF sug; glucose, fructose, sucrose 2:2:1) to meals not containing KF. The meals were flaked wheat biscuit (WB)+KFsug, WB+KF, WB+guar gum+KFsug, WB+guar gum+KF, that was ingested after fasting overnight. Blood glucose was monitored 3 h and hunger measured at 180 min post-meal using a visual analogue scale. KF and guar reduced postprandial blood glucose response amplitude, and prevented subsequent hypoglycaemia that occurred with WB+KFsug. The area between the blood glucose response curve and baseline from 0 to 180 min was not significantly different between meals, 0–120 min areas were significantly reduced by KF and/or guar. Area from 120 to 180 min was positive for KF, guar, and KF+guar, while the area for the WB meal was negative. Hunger at 180 min was significantly reduced by KF and/or guar when compared with WB. We conclude that KF components other than available carbohydrate may improve the glycaemic response profile to co-ingested cereal food. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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3269 KiB  
Article
The 1-Week and 8-Month Effects of a Ketogenic Diet or Ketone Salt Supplementation on Multi-Organ Markers of Oxidative Stress and Mitochondrial Function in Rats
by Wesley C. Kephart, Petey W. Mumford, Xuansong Mao, Matthew A. Romero, Hayden W. Hyatt, Yufeng Zhang, Christopher B. Mobley, John C. Quindry, Kaelin C. Young, Darren T. Beck, Jeffrey S. Martin, Danielle J. McCullough, Dominic P. D’Agostino, Ryan P. Lowery, Jacob M. Wilson, Andreas N. Kavazis and Michael D. Roberts
Nutrients 2017, 9(9), 1019; https://doi.org/10.3390/nu9091019 - 15 Sep 2017
Cited by 42 | Viewed by 10483
Abstract
We determined the short- and long-term effects of a ketogenic diet (KD) or ketone salt (KS) supplementation on multi-organ oxidative stress and mitochondrial markers. For short-term feedings, 4 month-old male rats were provided isocaloric amounts of KD (n = 10), standard chow [...] Read more.
We determined the short- and long-term effects of a ketogenic diet (KD) or ketone salt (KS) supplementation on multi-organ oxidative stress and mitochondrial markers. For short-term feedings, 4 month-old male rats were provided isocaloric amounts of KD (n = 10), standard chow (SC) (n = 10) or SC + KS (~1.2 g/day, n = 10). For long-term feedings, 4 month-old male rats were provided KD (n = 8), SC (n = 7) or SC + KS (n = 7) for 8 months and rotarod tested every 2 months. Blood, brain (whole cortex), liver and gastrocnemius muscle were harvested from all rats for biochemical analyses. Additionally, mitochondria from the brain, muscle and liver tissue of long-term-fed rats were analyzed for mitochondrial quantity (maximal citrate synthase activity), quality (state 3 and 4 respiration) and reactive oxygen species (ROS) assays. Liver antioxidant capacity trended higher in short-term KD- and SC + KS-fed versus SC-fed rats, and short-term KD-fed rats exhibited significantly greater serum ketones compared to SC + KS-fed rats indicating that the diet (not KS supplementation) induced ketonemia. In long term-fed rats: (a) serum ketones were significantly greater in KD- versus SC- and SC + KS-fed rats; (b) liver antioxidant capacity and glutathione peroxidase protein was significantly greater in KD- versus SC-fed rats, respectively, while liver protein carbonyls were lowest in KD-fed rats; and (c) gastrocnemius mitochondrial ROS production was significantly greater in KD-fed rats versus other groups, and this paralleled lower mitochondrial glutathione levels. Additionally, the gastrocnemius pyruvate-malate mitochondrial respiratory control ratio was significantly impaired in long-term KD-fed rats, and gastrocnemius mitochondrial quantity was lowest in these animals. Rotarod performance was greatest in KD-fed rats versus all other groups at 2, 4 and 8 months, although there was a significant age-related decline in performance existed in KD-fed rats which was not evident in the other two groups. In conclusion, short- and long-term KD improves select markers of liver oxidative stress compared to SC feeding, although long-term KD feeding may negatively affect skeletal muscle mitochondrial physiology. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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4521 KiB  
Article
LXRα Regulates Hepatic ChREBPα Activity and Lipogenesis upon Glucose, but Not Fructose Feeding in Mice
by Qiong Fan, Rikke C. Nørgaard, Christian Bindesbøll, Christin Lucas, Knut Tomas Dalen, Eshrat Babaie, Harri M. Itkonen, Jason Matthews, Hilde I. Nebb and Line M. Grønning-Wang
Nutrients 2017, 9(7), 678; https://doi.org/10.3390/nu9070678 - 29 Jun 2017
Cited by 18 | Viewed by 6044
Abstract
Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis. LXRα/β double knockout (LXRα−/−−/−) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, [...] Read more.
Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis. LXRα/β double knockout (LXRα−/−−/−) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis. However, the role of LXRs in fructose-induced ChREBP activation and lipogenesis is currently unknown. In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα−/−) mice. Hepatic lipogenic gene expression was reduced in glucose fed, but not fructose fed LXRα−/− mice. This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice. Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα−/− mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding. In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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Review

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21 pages, 1156 KiB  
Review
Regulation of Muscle Glycogen Metabolism during Exercise: Implications for Endurance Performance and Training Adaptations
by Mark A. Hearris, Kelly M. Hammond, J. Marc Fell and James P. Morton
Nutrients 2018, 10(3), 298; https://doi.org/10.3390/nu10030298 - 2 Mar 2018
Cited by 155 | Viewed by 46724
Abstract
Since the introduction of the muscle biopsy technique in the late 1960s, our understanding of the regulation of muscle glycogen storage and metabolism has advanced considerably. Muscle glycogenolysis and rates of carbohydrate (CHO) oxidation are affected by factors such as exercise intensity, duration, [...] Read more.
Since the introduction of the muscle biopsy technique in the late 1960s, our understanding of the regulation of muscle glycogen storage and metabolism has advanced considerably. Muscle glycogenolysis and rates of carbohydrate (CHO) oxidation are affected by factors such as exercise intensity, duration, training status and substrate availability. Such changes to the global exercise stimulus exert regulatory effects on key enzymes and transport proteins via both hormonal control and local allosteric regulation. Given the well-documented effects of high CHO availability on promoting exercise performance, elite endurance athletes are typically advised to ensure high CHO availability before, during and after high-intensity training sessions or competition. Nonetheless, in recognition that the glycogen granule is more than a simple fuel store, it is now also accepted that glycogen is a potent regulator of the molecular cell signaling pathways that regulate the oxidative phenotype. Accordingly, the concept of deliberately training with low CHO availability has now gained increased popularity amongst athletic circles. In this review, we present an overview of the regulatory control of CHO metabolism during exercise (with a specific emphasis on muscle glycogen utilization) in order to discuss the effects of both high and low CHO availability on modulating exercise performance and training adaptations, respectively. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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11 pages, 253 KiB  
Review
Carbohydrate Counting in Children and Adolescents with Type 1 Diabetes
by Giorgia Tascini, Maria Giulia Berioli, Laura Cerquiglini, Elisa Santi, Giulia Mancini, Francesco Rogari, Giada Toni and Susanna Esposito
Nutrients 2018, 10(1), 109; https://doi.org/10.3390/nu10010109 - 22 Jan 2018
Cited by 67 | Viewed by 19104
Abstract
Carbohydrate counting (CC) is a meal-planning tool for patients with type 1 diabetes (T1D) treated with a basal bolus insulin regimen by means of multiple daily injections or continuous subcutaneous insulin infusion. It is based on an awareness of foods that contain carbohydrates [...] Read more.
Carbohydrate counting (CC) is a meal-planning tool for patients with type 1 diabetes (T1D) treated with a basal bolus insulin regimen by means of multiple daily injections or continuous subcutaneous insulin infusion. It is based on an awareness of foods that contain carbohydrates and their effect on blood glucose. The bolus insulin dose needed is obtained from the total amount of carbohydrates consumed at each meal and the insulin-to-carbohydrate ratio. Evidence suggests that CC may have positive effects on metabolic control and on reducing glycosylated haemoglobin concentration (HbA1c). Moreover, CC might reduce the frequency of hypoglycaemia. In addition, with CC the flexibility of meals and snacks allows children and teenagers to manage their T1D more effectively within their own lifestyles. CC and the bolus calculator can have possible beneficial effects in improving post-meal glucose, with a higher percentage of values within the target. Moreover, CC might be integrated with the counting of fat and protein to more accurately calculate the insulin bolus. In conclusion, in children and adolescents with T1D, CC may have a positive effect on metabolic control, might reduce hypoglycaemia events, improves quality of life, and seems to do so without influencing body mass index; however, more high-quality clinical trials are needed to confirm this positive impact. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
15 pages, 420 KiB  
Review
Interstitial Glucose and Physical Exercise in Type 1 Diabetes: Integrative Physiology, Technology, and the Gap In-Between
by Othmar Moser, Jane E. Yardley and Richard M. Bracken
Nutrients 2018, 10(1), 93; https://doi.org/10.3390/nu10010093 - 15 Jan 2018
Cited by 47 | Viewed by 11123
Abstract
Continuous and flash glucose monitoring systems measure interstitial fluid glucose concentrations within a body compartment that is dramatically altered by posture and is responsive to the physiological and metabolic changes that enable exercise performance in individuals with type 1 diabetes. Body fluid redistribution [...] Read more.
Continuous and flash glucose monitoring systems measure interstitial fluid glucose concentrations within a body compartment that is dramatically altered by posture and is responsive to the physiological and metabolic changes that enable exercise performance in individuals with type 1 diabetes. Body fluid redistribution within the interstitial compartment, alterations in interstitial fluid volume, changes in rate and direction of fluid flow between the vasculature, interstitium and lymphatics, as well as alterations in the rate of glucose production and uptake by exercising tissues, make for caution when interpreting device read-outs in a rapidly changing internal environment during acute exercise. We present an understanding of the physiological and metabolic changes taking place with acute exercise and detail the blood and interstitial glucose responses with different forms of exercise, namely sustained endurance, high-intensity, and strength exercises in individuals with type 1 diabetes. Further, we detail novel technical information on currently available patient devices. As more health services and insurance companies advocate their use, understanding continuous and flash glucose monitoring for its strengths and limitations may offer more confidence for patients aiming to manage glycemia around exercise. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
222 KiB  
Review
Carbohydrates for Soccer: A Focus on Skilled Actions and Half-Time Practices
by Samuel P. Hills and Mark Russell
Nutrients 2018, 10(1), 22; https://doi.org/10.3390/nu10010022 - 25 Dec 2017
Cited by 21 | Viewed by 13028
Abstract
Carbohydrate consumption is synonymous with soccer performance due to the established effects on endogenous energy store preservation, and physical capacity maintenance. For performance-enhancement purposes, exogenous energy consumption (in the form of drinks, bars, gels and snacks) is recommended on match-day; specifically, before and [...] Read more.
Carbohydrate consumption is synonymous with soccer performance due to the established effects on endogenous energy store preservation, and physical capacity maintenance. For performance-enhancement purposes, exogenous energy consumption (in the form of drinks, bars, gels and snacks) is recommended on match-day; specifically, before and during match-play. Akin to the demands of soccer, limited opportunities exist to consume carbohydrates outside of scheduled breaks in competition, such as at half-time. The link between cognitive function and blood glucose availability suggests that carbohydrates may influence decision-making and technical proficiency (e.g., soccer skills). However, relatively few reviews have focused on technical, as opposed to physical, performance while also addressing the practicalities associated with carbohydrate consumption when limited in-play feeding opportunities exist. Transient physiological responses associated with reductions in activity prevalent in scheduled intra-match breaks (e.g., half-time) likely have important consequences for practitioners aiming to optimize match-day performance. Accordingly, this review evaluated novel developments in soccer literature regarding (1) the ergogenic properties of carbohydrates for skill performance; and (2) novel considerations concerning exogenous energy provision during half-time. Recommendations are made to modify half-time practices in an aim to enhance subsequent performance. Viable future research opportunities exist regarding a deeper insight into carbohydrate provision on match-day. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
1001 KiB  
Review
Metabolic Effects of High Glycaemic Index Diets: A Systematic Review and Meta-Analysis of Feeding Studies in Mice and Rats
by Grace J. Campbell, Alistair M. Senior and Kim S. Bell-Anderson
Nutrients 2017, 9(7), 646; https://doi.org/10.3390/nu9070646 - 22 Jun 2017
Cited by 20 | Viewed by 7001
Abstract
Low glycaemic index (LGI) diets are often reported to benefit metabolic health, but the mechanism(s) responsible are not clear. This review aimed to systematically identify studies investigating metabolic effects of high glycaemic index (HGI) versus LGI diets in mice and rats. A meta-analysis [...] Read more.
Low glycaemic index (LGI) diets are often reported to benefit metabolic health, but the mechanism(s) responsible are not clear. This review aimed to systematically identify studies investigating metabolic effects of high glycaemic index (HGI) versus LGI diets in mice and rats. A meta-analysis was conducted to calculate an overall effect size, Hedge’s standardised mean differences (hereafter d), for each trait, with moderator variables considered in subsequent meta-regressions. Across 30 articles, a HGI diet increased five of the seven traits examined: body weight (d = 0.55; 95% confidence interval: 0.31, 0.79), fat mass (d = 1.08; 0.67, 1.49), fasting circulating insulin levels (d = 0.40; 0.09, 0.71), and glucose (d = 0.80; 0.35, 1.25) and insulin (d = 1.14; 0.50, 1.77) area under the curve during a glucose tolerance test. However, there was substantial heterogeneity among the effects for all traits and the small number of studies enabled only limited investigation of possible confounding factors. HGI diets favour body weight gain, increased adiposity and detrimentally affect parameters of glucose homeostasis in mice and rats, but these effects may not be a direct result of GI per se; rather they may be due to variation in other dietary constituents, such as dietary fibre, a factor which is known to reduce the GI of food and promote health via GI-independent mechanisms. Full article
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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