Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome.

The prevalence of metabolic syndrome (MetS) is increasing, and patients with MetS are at an increased risk of cardiovascular disease and diabetes. There is a close link between hypomagnesemia and MetS. Administration of sodium-glucose transporter 2 (SGLT2) inhibitors has been reported to increase serum magnesium levels in patients with diabetes. We investigated the alterations in renal magnesium handling in an animal model of MetS and analyzed the effects of SGLT2 inhibitors. Adult rats were fed a fructose-rich diet to induce MetS in the first 3 months and were then treated with either dapagliflozin or magnesium sulfate-containing drinking water for another 3 months. Fructose-fed animals had increased insulin resistance, hypomagnesemia, and decreased urinary magnesium excretion. Dapagliflozin treatment improved insulin resistance by decreasing glucose and insulin levels, increased serum magnesium levels, and reduced urinary magnesium excretion. Serum vitamin D and parathyroid hormone levels were decreased in fructose-fed animals, and the levels remained low despite dapagliflozin and magnesium supplementation. In the kidney, claudin-16, TRPM6/7, and FXDY expression was increased in fructose-fed animals. Dapagliflozin increased intracellular magnesium concentration, and this effect was inhibited by TRPM6 blockade and the EGFR antagonist. We concluded that high fructose intake combined with a low-magnesium diet induced MetS and hypomagnesemia. Both dapagliflozin and magnesium sulfate supplementation improved the features of MetS and increased serum magnesium levels. Expression levels of magnesium transporters such as claudin-16, TRPM6/7, and FXYD2 were increased in fructose-fed animals and in those administered dapagliflozin and magnesium sulfate. Dapagliflozin enhances TRPM6-mediated trans-epithelial magnesium transport in renal tubule cells.

Acute Metabolic Responses to Glucose and Fructose Supplementation in Healthy Individuals: A Double-Blind Randomized Crossover Placebo-Controlled Trial.

The aim of this study was to investigate the impact of glucose (Glu), fructose (Fru), glucose and fructose (GluFru) and sucralose on blood glucose response in healthy individuals. Fifteen healthy individuals (five females, age of 25.4 ± 2.5 years, BMI of 23.7 ± 1.7 kg/m2 with a body mass (BM) of 76.3 ± 12.3 kg) participated in this double-blind randomized crossover placebo-controlled trial. Participants received a mixture of 300 mL of water with 1 g/kg BM of Glu, 1 g/kg BM of Fru, 0.5 g/kg BM of GluFru (each), and 0.2 g sucralose as a placebo. Peak BG values Glu were reached after 40 ± 13 min (peak BG: 141 ± 20 mg/dL), for Fru after 36 ± 22 min (peak BG: 98 ± 7 mg/dL), for GluFru after 29 ± 8 min (BG 128 ± 18 mg/dL), and sucralose after 34 ± 27 min (peak BG: 83 ± 5 mg/dL). Significant differences regarding the time until peak BG were found only between Glu and GluFru supplementation (p = 0.02). Peak blood glucose levels were significantly lower following the ingestion of Fru compared to the supplementation of Glu and GluFru (p < 0.0001) while Glu and GluFru supplementation showed no difference in peak values (p = 0.23). All conditions led to a significantly higher peak BG value compared to sucralose (p < 0.0001). Blood lactate increased in Glu (p = 0.002), Fru and GluFru (both p < 0.0001), whereas sucralose did not increase compared to the baseline (p = 0.051). Insulin levels were significantly higher in all conditions at peak compared to sucralose (p < 0.0001). The findings of this study prove the feasibility of combined carbohydrate supplementations for many applications in diabetic or healthy exercise cohorts.

Isorhamnetin attenuates high-fat and high-fructose diet induced cognitive impairments and neuroinflammation by mediating MAPK and NFκB signaling pathways.

Isorhamnetin (ISO), a flavonoid compound isolated from sea-buckthorn (Hippophae rhamnoides L.) fruit, has anti-inflammatory effects. However, the effects of ISO on neuroinflammation and cognitive function are still unclear. The purpose of this study was to evaluate the protective effect of ISO on cognitive impairment in obese mice induced by a high-fat and high fructose diet (HFFD). It has been found that oral administration of ISO (0.03% w/w and 0.06% w/w) for 14 weeks significantly reduced the body weight, food intake, liver weight, liver lipid level, and serum lipid level of HFFD-fed mice. ISO can also significantly prevent HFFD-induced neuronal working, spatial, and long-term memory impairment. Notably, the ISO treatment activated the CREB/BDNF pathway and increased neurotrophic factors in the brains of mice. Furthermore, ISO inhibited HFFD-induced microglial overactivation and down-regulated inflammatory cytokines in both serum and the brain. It can also inhibit the expression of p-JNK, p-p38, and p-NFκB protein in the mouse brain. In conclusion, these results indicated that ISO mitigated HFFD-induced cognitive impairments by inhibiting the MAPK and NFκB signaling pathways, suggesting that ISO might be a plausible nutritional intervention for metabolic syndrome-related cognitive complications.

Kombuchas from green and black teas reduce oxidative stress, liver steatosis and inflammation, and improve glucose metabolism in Wistar rats fed a high-fat high-fructose diet.

The aim of this study was to evaluate the effect of green and black tea kombuchas consumption on adiposity, lipid and glucose metabolism, liver steatosis, oxidative stress, and inflammation in Wistar rats fed a high-fat high-fructose (HFHF) diet. Wistar rats, after 8 weeks to induce metabolic alterations, were divided into an AIN-93M control group, HFHF control group, green tea kombucha + HFHF diet (GTK group), and black tea kombucha + HFHF diet (BTK group), for 10 weeks. The kombuchas improved glucose metabolism, plasma total antioxidant capacity, superoxide dismutase activity, and decreased nitric oxide concentration. Moreover, both kombuchas reduced systemic inflammation by decreasing the neutrophil/lymphocyte ratio (NLR), reduced the total adipose tissue and blood triglyceride, and reverted liver steatosis (from grade 2 to 1), besides the modulation of genes related to adipogenesis and ß-oxidation. Therefore, kombuchas from green and black teas have bioactive properties that can help control metabolic alterations induced by the HFHF diet.

Comparative impact of dietary carbohydrates on the liver transcriptome in two strains of mice.

Excessive long-term consumption of dietary carbohydrates, including glucose, sucrose, or fructose, has been shown to have significant impact on genome-wide gene expression, which likely results from changes in metabolic substrate flux. However, there has been no comprehensive study on the acute effects of individual sugars on the genome-wide gene expression that may reveal the genetic changes altering signaling pathways, subsequent metabolic processes, and ultimately physiological/pathological responses. Considering that gene expressions in response to acute carbohydrate ingestion might be different in nutrient sensitive and insensitive mammals, we conducted comparative studies of genome-wide gene expression by deep mRNA sequencing of the liver in nutrient sensitive C57BL/6J and nutrient insensitive BALB/cJ mice. Furthermore, to determine the temporal responses, we compared livers from mice in the fasted state and following ingestion of standard laboratory mouse chow supplemented with plain drinking water or water containing 20% glucose, sucrose, or fructose. Supplementation with these carbohydrates induced unique extents and temporal changes in gene expressions in a strain specific manner. Fructose and sucrose stimulated gene changes peaked at 3 h postprandial, whereas glucose effects peaked at 12 h and 6 h postprandial in C57BL/6J and BABL/cJ mice, respectively. Network analyses revealed that fructose changed genes were primarily involved in lipid metabolism and were more complex in C57BL/6J than in BALB/cJ mice. These data demonstrate that there are qualitative and antitative differences in the normal physiological responses of the liver between these two strains of mice and C57BL/6J is more sensitive to sugar intake than BALB/cJ.

Effects of two different doses of carbohydrate ingestion on taekwondo-related performance during a simulated tournament.

BACKGROUND: Carbohydrate (CHO) ingestion enhances exercise performance; however, the efficacy of CHO intake on repeated bouts of exercise simulating a taekwondo tournament is unknown. Therefore, the purpose was to compare the effects of two different doses of CHO on a sports-specific kicking test during a simulated taekwondo tournament compared to placebo (PLA). METHODS: In a double-blind, randomized-placebo controlled, cross-over trial, eleven junior male professional taekwondo athletes (age: 16 ± 0.8 years, body mass: 55.3 ± 7.3 kg) ingested one of three solutions: (i) high dose (C45): 45 g of CHO (60 g∙h- 1), (ii) low dose (C22.5): 22.5 g of CHO (30 g∙h- 1; both solutions containing 2:1 glucose:fructose), or a PLA immediately following each kicking test. The kicking test was repeated 5 times, separated by 45 mins of rest, simulating a typical taekwondo competition day. Ratings of perceived exertion (RPE) and gastrointestinal discomfort (GI) scores were collected immediately after, and blood glucose before each test. RESULTS: The results revealed that C45 and C22.5 did not improve total, successful, or percentage of successful kicks compared to PLA (p > 0.05). Blood glucose was significantly higher following both CHO conditions compared with PLA across all five tests (p < 0.05). There were no differences between treatments or across tests for RPE (p > 0.05). CONCLUSION: CHO intake, independent of the dose, did not alter taekwondo kick performance during a simulated taekwondo tournament.

Dietary supplementation with myo-inositol reduces high-fructose diet-induced hepatic ChREBP binding and acetylation of histones H3 and H4 on the Elovl6 gene in rats.

ELOVL fatty acid elongase 6 (ELOVL6) is a long-chain fatty acid elongase, and the hepatic expression of the Elovl6 gene and accumulation of triglycerides (TG) are enhanced by long-term high-fructose intake. Fatty acid synthesis genes, including Elovl6, are regulated by lipogenic transcription factors, sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP). In addition, carbohydrate signals induce the expression of fatty acid synthase not only via these transcription factors but also via histone acetylation. Since a major lipotrope, myo-inositol (MI), can repress short-term high-fructose-induced fatty liver and the expression of fatty acid synthesis genes, we hypothesized that MI might influence SREBP-1c, ChREBP, and histone acetylation of Elovl6 in fatty liver induced by even short-term high-fructose intake. This study aimed to investigate whether dietary supplementation with MI affects Elovl6 expression, SREBP-1 and ChREBP binding, and acetylation of histones H3 and H4 at the Elovl6 promoter in short-term high-fructose diet-induced fatty liver in rats. Rats were fed a control diet, high-fructose diet, or high-fructose diet supplemented with 0.5% MI for 10 days. This study showed that MI supplementation reduced short-term high-fructose diet-induced hepatic expression of the Elovl6 gene, ChREBP binding, but not SREBP-1 binding, and acetylation of histones H3 and H4 at the Elovl6 promoter.

Sasa quelpaertensis Leaf Extract Ameliorates Dyslipidemia, Insulin Resistance, and Hepatic Lipid Accumulation in High-Fructose-Diet-Fed Rats.

BACKGROUND: Increased dietary fructose consumption is closely associated with lipid and glucose metabolic disorders. Sasa quelpaertensis Nakai possesses various health-promoting properties, but there has been no research on its protective effect against fructose-induced metabolic dysfunction. In this study, we investigated the effects of S. quelpaertensis leaf extract (SQE) on metabolic dysfunction in high-fructose-diet-fed rats. METHODS: Animals were fed a 46% carbohydrate diet, a 60% high-fructose diet, or a 60% high-fructose diet with SQE (500 mg/kg of body weight (BW)/day) in drinking water for 16 weeks. Serum biochemical parameters were measured and the effects of SQE on hepatic histology, protein expression, and transcriptome profiles were investigated. RESULTS: SQE improved dyslipidemia and insulin resistance induced in high-fructose-diet-fed rats. SQE ameliorated the lipid accumulation and inflammatory response in liver tissues by modulating the expressions of key proteins related to lipid metabolism and antioxidant response. SQE significantly enriched the genes related to the metabolic pathway, namely, the tumor necrosis factor (TNF) signaling pathway and the PI3K-Akt signaling pathway. CONCLUSIONS: SQE could effectively prevent dyslipidemia, insulin resistance, and hepatic lipid accumulation by regulation of metabolism-related gene expressions, suggesting its role as a functional ingredient to prevent lifestyle-related metabolic disorders.

Fructose-Induced Intestinal Microbiota Shift Following Two Types of Short-Term High-Fructose Dietary Phases.

High consumption of fructose and high-fructose corn syrup is related to the development of obesity-associated metabolic diseases, which have become the most relevant diet-induced diseases. However, the influences of a high-fructose diet on gut microbiota are still largely unknown. We therefore examined the effect of short-term high-fructose consumption on the human intestinal microbiota. Twelve healthy adult women were enrolled in a pilot intervention study. All study participants consecutively followed four different diets, first a low fructose diet (< 10 g/day fructose), then a fruit-rich diet (100 g/day fructose) followed by a low fructose diet (10 g/day fructose) and at last a high-fructose syrup (HFS) supplemented diet (100 g/day fructose). Fecal microbiota was analyzed by 16S rRNA sequencing. A high-fructose fruit diet significantly shifted the human gut microbiota by increasing the abundance of the phylum Firmicutes, in which beneficial butyrate producing bacteria such as Faecalibacterium, Anareostipes and Erysipelatoclostridium were elevated, and decreasing the abundance of the phylum Bacteroidetes including the genus Parabacteroides. An HFS diet induced substantial differences in microbiota composition compared to the fruit-rich diet leading to a lower Firmicutes and a higher Bacteroidetes abundance as well as reduced abundance of the genus Ruminococcus. Compared to a low-fructose diet we observed a decrease of Faecalibacterium and Erysipelatoclostridium after the HFS diet. Abundance of Bacteroidetes positively correlated with plasma cholesterol and LDL level, whereas abundance of Firmicutes was negatively correlated. Different formulations of high-fructose diets induce distinct alterations in gut microbiota composition. High-fructose intake by HFS causes a reduction of beneficial butyrate producing bacteria and a gut microbiota profile that may affect unfavorably host lipid metabolism whereas high consumption of fructose from fruit seems to modulate the composition of the gut microbiota in a beneficial way supporting digestive health and counteracting harmful effects of excessive fructose.

Effects of a Low Dose of Caffeine Alone or as Part of a Green Coffee Extract, in a Rat Dietary Model of Lean Non-Alcoholic Fatty Liver Disease without Inflammation.

Non-alcoholic fatty liver disease is a highly prevalent condition without specific pharmacological treatment, characterized in the initial stages by hepatic steatosis. It was suggested that lipid infiltration in the liver might be reduced by caffeine through anti-inflammatory, antioxidative, and fatty acid metabolism-related mechanisms. We investigated the effects of caffeine (CAF) and green coffee extract (GCE) on hepatic lipids in lean female rats with steatosis. For three months, female Sprague-Dawley rats were fed a standard diet or a cocoa butter-based high-fat diet plus 10% liquid fructose. In the last month, the high-fat diet was supplemented or not with CAF or a GCE, providing 5 mg/kg of CAF. Plasma lipid levels and the hepatic expression of molecules involved in lipid metabolism were determined. Lipidomic analysis was performed in liver samples. The diet caused hepatic steatosis without obesity, inflammation, endoplasmic reticulum stress, or hepatic insulin resistance. Neither CAF nor GCE alleviated hepatic steatosis, but GCE-treated rats showed lower hepatic triglyceride levels compared to the CAF group. The GCE effects could be related to reductions of hepatic (i) mTOR phosphorylation, leading to higher nuclear lipin-1 levels and limiting lipogenic gene expression; (ii) diacylglycerol levels; (iii) hexosylceramide/ceramide ratios; and (iv) very-low-density lipoprotein receptor expression. In conclusion, a low dose of CAF did not reduce hepatic steatosis in lean female rats, but the same dose provided as a green coffee extract led to lower liver triglyceride levels.

Maternal fish oil supplementation ameliorates maternal high-fructose diet-induced dyslipidemia in neonatal mice with suppression of lipogenic gene expression in livers of postpartum mice.

Maternal fructose consumption during pregnancy and lactation is associated with metabolic dysregulation in offspring. We tested the hypothesis that fish oil (FO) supplementation during pregnancy and lactation improves fructose-induced metabolic dysregulation in postpartum dams and offspring mice. We therefore aimed to determine the effects of FO supplementation on metabolic disruption in neonatal mice and dams induced by a maternal high-fructose diet (HFrD). The weight of the offspring of dams fed with HFrD on postnatal day 5 was significantly low, but this was reversed by adding FO to the maternal diet. Feeding dams with HFrD significantly increased plasma concentrations of triglycerides, uric acid, and total cholesterol, and decreased free fatty acid concentrations in offspring. Maternal supplementation with FO significantly suppressed HFrD-induced hypertriglyceridemia and hyperuricemia in the offspring. Maternal HFrD induced remarkable mRNA expression of the lipogenic genes Srebf1, Fasn, Acc1, Scd1, and Acly in the postpartum mouse liver without affecting hepatic and plasma lipid levels. Although expression levels of lipogenic genes were higher in the livers of postpartum dams than in those of nonmated mice, HFrD feeding increased the hepatic lipid accumulation in nonmated mice but not in postpartum dams. These findings suggest that although hepatic lipogenic activity is higher in postpartum dams than nonmated mice, the lipid consumption is enhanced in postpartum dams during pregnancy and lactation. Maternal FO supplementation obviously suppressed the expression of these lipogenic genes. These findings coincide with reduced plasma triglyceride concentrations in the offspring. Therefore, dietary FO apparently ameliorated maternal HFrD-induced dyslipidemia in offspring by suppressing maternal lipogenic gene expression and/or neonatal plasma levels of uric acid.

Metabolite profiling of mice under long-term fructose drinking and vitamin D deficiency: increased risks for metabolic syndrome and nonalcoholic fatty liver disease.

Chronic fructose consumption and vitamin D deficiency (VDD) diet have been linked to the pandemic of metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD). The metabolic mechanisms remain unclear. This study is to explore metabolic changes of mice fed with high fructose syrup and VDD diet in the biogenesis of MetS and NAFLD. C57BL/6J mice were treated with four conditions for 28 weeks: control (standard chow and sterile water), fructose drinking (FD, standard chow and 20 g/100 mL fructose in drinking water), VDD (standard chow with VD depleted and sterile water), and FD+VDD. Metabolites in the serum and liver of mice were analyzed by gas chromatography-mass spectrometry combined with trimethylsilyl derivatization. The histological results indicated that one-hit from long-term fructose drinking led to mild MetS, and a combination with VDD diet induced hepatic steatosis, inflammatory lesion, and interstitial fibrosis in mice, showing significant nonalcoholic steatohepatitis features. Metabolomics analysis showed significant changes in amino acids and short-chain organic acids in response to fructose drinking. VDD diet led to significant increase of hepatic fatty acids, which was consistent with the hepatic morphology of fat deposition. This work demonstrated a concert effect of FD and VDD in promoting MetS and NAFLD through changing in vivo metabolism and signaling pathways. And metabolomics analysis could provide early warnings for the biogenesis of MetS and NAFLD. Importantly, vitamin D supplementation in the diet can balance the metabolic disorders caused by excessive fructose intake.

Anti-Diabetic Effects of Allulose in Diet-Induced Obese Mice via Regulation of mRNA Expression and Alteration of the Microbiome Composition.

Allulose has been reported to serve as an anti-obesity and anti-diabetic food component; however, its molecular mechanism is not yet completely understood. This study aims to elucidate the mechanisms of action for allulose in obesity-induced type 2 diabetes mellitus (T2DM), by analyzing the transcriptional and microbial populations of diet-induced obese mice. Thirty-six C57BL/6J mice were divided into four groups, fed with a normal diet (ND), a high-fat diet (HFD), a HFD supplemented with 5% erythritol, or a HFD supplemented with 5% allulose for 16 weeks, in a pair-fed manner. The allulose supplement reduced obesity and comorbidities, including inflammation and hepatic steatosis, and changed the microbial community in HFD-induced obese mice. Allulose attenuated obesity-mediated inflammation, by downregulating mRNA levels of inflammatory response components in the liver, leads to decreased plasma pro-inflammatory marker levels. Allulose suppressed glucose and lipid metabolism-regulating enzyme activities, ameliorating hepatic steatosis and improving dyslipidemia. Allulose improved fasting blood glucose (FBG), plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), and the area under the curve (AUC) for the intraperitoneal glucose tolerance test (IPGTT), as well as hepatic lipid levels. Our findings suggested that allulose reduced HFD-induced obesity and improved T2DM by altering mRNA expression and the microbiome community.

Substitution of high-dose sucrose with fructose in high-fat diets resulted in higher plasma concentrations of aspartic acid, cystine, glutamic acid, ornithine and phenylalanine, and higher urine concentrations of arginine and citrulline.

High fructose intake has been shown to increase circulating alanine transaminase in humans, which could reflect damage to the liver by fructose but could also be linked to higher level of transamination of amino acids in liver. Therefore, we hypothesized that a diet with high content of fructose would affect the amino acid composition in rat plasma and urine differently from a diet with high sucrose content. Because high intake of sucrose and fructose is often accompanied with high intake of saturated fat in the Western-style diet, we wanted to compare the effects of high fructose/sucrose in diets with normal or high content of coconut oil on individual free amino acids plasma and urine. Male Wistar rats were fed diets with normal (10 wt%) or high (40 wt%) content of sucrose or fructose, with normal or high fat content (7 or 22 wt%) and 20 wt% protein (casein). Rats fed high-fructose high-fat diet had higher plasma concentrations of aspartic acid, cystine, glutamic acid, ornithine, and phenylalanine and higher urine concentrations of arginine and citrulline when compared to rats fed high-sucrose high-fat diet. Substituting normal content of sucrose with fructose in the diets had little impact on amino acids in plasma and urine. Serum concentrations of alanine transaminase, aspartate transaminase, and creatinine, and urine cystatin C and T cell immunoglobulin mucin-1 concentrations were comparable between the groups and within normal ranges. To conclude, substituting high-dose sucrose with high-dose fructose in high-fat diets affected amino acid compositions in plasma and urine.

Effect of omega-3 fatty acids on glucose homeostasis: role of free fatty acid receptor 1.

Insulin resistance is a worldwide health problem. This study investigated the acute effects of eicosapentanoic acid (EPA) on glucose homeostasis focusing on the role of free fatty acid receptor 1 (FFAR1) and the chronic effects of fish oil omega-3 fatty acids on insulin resistance. Insulin resistance was induced by feeding mice high-fructose, high-fat diet (HFrHFD) for 16 weeks. In the first part, the acute effects of EPA alone and in combination with GW1100 and DC260126 (FFAR1 blockers) on glucose homeostasis and hepatic phosphatidyl-inositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) were investigated in standard chow diet (SCD)- and HFrHFD-fed mice. In the second part, mice were treated with fish oil omega-3 fatty acids for 4 weeks starting at the week 13 of feeding HFrHFD. Changes in the blood- and liver tissue-insulin resistance markers and FFAR1 downstream signals were recorded at the end of experiment. Results showed that EPA increased 0 and 30 min blood glucose levels after glucose load in SCD-fed mice but improved glucose tolerance in HFrHFD-fed mice. Moreover, FFAR1 blockers reduced EPA effects on glucose tolerance and hepatic PIP2 and DAG levels. On the other hand, chronic use of fish oil omega-3 fatty acids increased FBG levels and decreased serum insulin and triglycerides levels without improving the index of insulin resistance. Also, they increased hepatic ß-arrestin-2, PIP2, and pS473 Akt levels but decreased DAG levels. In conclusion, EPA acutely improved glucose homeostasis in HFrHFD-fed mice by modulating the activity of FFAR1. However, the chronic use of fish oil omega-3 fatty acids did not improve the insulin resistance.

Addition of pectin-alginate to a carbohydrate beverage does not maintain gastrointestinal barrier function during exercise in hot-humid conditions better than carbohydrate ingestion alone.

The objective of this study was to compare the effects of consuming a 16% maltodextrin+fructose+pectin-alginate (MAL+FRU+PEC+ALG) drink against a nutrient-matched maltodextrin+fructose (MAL+FRU) drink on enterocyte damage and gastrointestinal permeability after cycling in hot and humid conditions. Fourteen recreational cyclists (7 men) completed 3 experimental trials in a randomized placebo-controlled design. Participants cycled for 90 min (45% maximal aerobic capacity) and completed a 15-min time-trial in hot (32 °C) humid (70% relative humidity) conditions. Every 15 min, cyclists consumed 143 mL of either (i) water; (ii) MAL+FRU+PEC+ALG (90 g·h-1 CHO/16% w/v); or (iii) a ratio-matched MAL+FRU drink (90 g·h-1 CHO/16% w/v). Blood was sampled before and after exercise and gastrointestinal (GI) permeability, which was determined by serum measurements of intestinal fatty acid binding protein (I-FABP) and the percent ratio of lactulose (5 g) to rhamnose (2 g) recovered in postexercise urine. Compared with water, I-FABP decreased by 349 ± 67pg·mL-1 with MAL+FRU+PEC+ALG (p = 0.007) and by 427 ± 56 pg·mL-1 with MAL+FRU (p = 0.02). GI permeability was reduced in both the MAL+FRU+PEC+ALG (by 0.019 ± 0.01, p = 0.0003) and MAL+FRU (by 0.014 ± 0.01, p = 0.002) conditions relative to water. In conclusion, both CHO beverages attenuated GI barrier damage to a similar extent relative to water. No metabolic, cardiovascular, thermoregulatory, or performance differences were observed between the CHO beverages. Novelty Consumption of multiple-transportable CHO, with or without hydrogel properties, preserves GI barrier integrity and reduces enterocyte damage during prolonged cycling in hot-humid conditions.

Thyme oxymel by improving of inflammation, oxidative stress, dyslipidemia and homeostasis of some trace elements ameliorates obesity induced by high-fructose/fat diet in male rat.

OBJECTIVE: Thyme oxymel is a mixture of vinegar, sugar and thyme which is traditionally used in many folk medicines as syrup to treat metabolic disorders. The molecular mechanisms of anti-hyperlipidemic and anti-inflammatory and antioxidant effects of thyme oxymel or oxymel and its role on homeostasis of trace elements are not fully understood. The aim of this study was to evaluate the anti-inflammatory, antioxidant and anti- hyperlipidemic effects of different doses of thyme oxymel and oxymel on obesity induced by high-fat/-fructose diet (HFFD) in male rat. METHODS: Eighty adult male Sprague-Dawley rats were randomly divided into eleven groups and treated daily for 24 weeks. At the end of the study, serum levels of liver enzymes, lipid profiles, blood glucose, insulin, antioxidant enzymes and lipid peroxidation and TNF-α were measured. The hepatic oxidative biomarkers and the genes expression of SREBP-1c, CPT-1, Nrf-2 and NF-κB were also studied to determine the molecular mechanism involved in this disease. RESULTS: The results showed that HFFD could significantly change the level of oxidative biomarkers, lipid profiles, TNF-α, liver enzymes, leptin, insulin and the levels of some trace elements in obese rats compared to control group (p < 0.05), while pretreatment and treatment with thyme oxymel and oxymel in obese rats could significantly ameliorate them and bring some of them back to normal (p < 0.05).The molecular results also showed that HFFD significantly up-regulated the expression of SREBP-1c and NF-κB and down-regulated CPT-1 and Nrf-2 expression(p < 0.05). While, pretreatment and treatment with thyme oxymel or oxymel in obese rats could significantly ameliorate them (p < 0.05). CONCLUSIONS: It can be concluded that thyme oxymel or oxymel can alleviate HFFD-induced obesity through improving oxidative stress, inflammation, lipid metabolism, homeostasis of some trace elements, and weight-regulating hormones.

Alteration of Microbiome Profile by D-Allulose in Amelioration of High-Fat-Diet-Induced Obesity in Mice.

Recently, there has been a global shift in diet towards an increased intake of energy-dense foods that are high in sugars. D-allulose has received attention as a sugar substitute and has been reported as one of the anti-obesity food components; however, its correlation with the intestinal microbial community is not yet completely understood. Thirty-six C57BL/6J mice were divided in to four dietary groups and fed a normal diet (ND), a high-fat diet (HFD, 20% fat, 1% cholesterol, w/w), and a HFD with 5% erythritol (ERY) and D-allulose (ALL) supplement for 16 weeks. A pair-feeding approach was used so that all groups receiving the high-fat diet would have the same calorie intake. As a result, body weight and body fat mass in the ALL group were significantly decreased toward the level of the normal group with a simultaneous decrease in plasma leptin and resistin. Fecal short-chain fatty acid (SCFA) production analysis revealed that ALL induced elevated total SCFA production compared to the other groups. Also, ALL supplement induced the change in the microbial community that could be responsible for improving the obesity based on 16S rRNA gene sequence analysis, and ALL significantly increased the energy expenditure in Day(6a.m to 6pm). Taken together, our findings suggest that 5% dietary ALL led to an improvement in HFD-induced obesity by altering the microbiome community.

Rhodiola crenulata root extract ameliorates fructose-induced hepatic steatosis in rats: Association with activating autophagy.

BACKGROUND: Increasing evidence has shown the beneficial effects of Rhodiola species on metabolic disorders, but their mechanisms are not clear. Hepatic steatosis is closely related to metabolic disorders, we aim to investigate the therapeutic effects of Rhodiola crenulata root (RCR) on fructose-induced hepatic steatosis and explore the underlying mechanisms. PURPOSE: To observe the effect of Rhodiola crenulata root extract (RCR) on fructose-induced hepatic steatosis in Sprague-Dawley (SD) rats and explore its possible mechanism. METHODS: Male Sprague-Dawley rats were treated with liquid fructose in their drinking water over 18 weeks. The extract of RCR was co-administered (once daily by oral gavage) during the last 5 weeks. Liver lipid deposition and morphological changes were observed by Oil red O staining. Real-time fluorescence quantitative PCR, Western blot and immunoprecipitation were used to detect gene and protein expression in liver. RESULTS: RCR (50 mg/kg) reversed liquid fructose-induced increase in hepatic triglyceride content in rats. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in RCR-treated rats. However, RCR treatment did not affect chow intake and body weight of rats. Although some genes of the pathways involved in DNL (ChREBP, SREBP-1c, FAS, ACC1, SCD1, DGAT1, DGAT2 and MGAT2), fatty acid ß-oxidation (PPARα, CPT1a, ACO and FGF21), VLDL-export (MTTP) and decomposition (HSL, ATGL) in the liver of fructose-fed rats were not changed significantly after RCR administration, the decrease in PPARα and PGC-1α proteins was reversed by RCR. Notably, SIRT1 mRNA and protein expression increased significantly with RCR administration. Furthermore, RCR increased expression of ATG4B, Beclin1 and decreased expression of Bcl2-Beclin1 complex dramatically. Meanwhile, RCR decreased the acetylation of beclin1. Moreover, RCR increased expression of autophagosome markers including LC3B and ATG5-ATG12-ATG16L1, and decreased expression of autophagolysosome marker p62 in the livers of fructose-fed rats. CONCLUSIONS: RCR has a certain improvement effect on fructose-induced hepatic steatosis, which is related to the activation of autophagy.

Pectin-Alginate Does Not Further Enhance Exogenous Carbohydrate Oxidation in Running.

PURPOSE: Maximizing carbohydrate availability is important for many endurance events. Combining pectin and sodium alginate with ingested maltodextrin-fructose (MAL + FRU + PEC + ALG) has been suggested to enhance carbohydrate delivery via hydrogel formation, but the influence on exogenous carbohydrate oxidation remains unknown. The primary aim of this study was to assess the effects of MAL + FRU + PEC + ALG on exogenous carbohydrate oxidation during exercise compared with a maltodextrin-fructose mixture (MAL + FRU). MAL + FRU has been well established to increase exogenous carbohydrate oxidation during cycling compared with glucose-based carbohydrates (MAL + GLU). However, much evidence focuses on cycling, and direct evidence in running is lacking. Therefore, a secondary aim was to compare exogenous carbohydrate oxidation rates with MAL + FRU versus MAL + GLU during running. METHODS: Nine trained runners completed two trials (MAL + FRU and MAL + FRU + PEC + ALG) in a double-blind, randomized crossover design. A subset (n = 7) also completed a MAL + GLU trial to address the secondary aim, and a water trial to establish background expired CO2 enrichment. Participants ran at 60% V˙O2peak for 120 min while ingesting either water only or carbohydrate solutions at a rate of 1.5 g carbohydrate per minute. RESULTS: At the end of 120 min of exercise, exogenous carbohydrate oxidation rates were 0.9 (SD 0.5) g·min with MAL + GLU ingestion. MAL + FRU ingestion increased exogenous carbohydrate oxidation rates to 1.1 (SD 0.3) g·min (P = 0.038), with no further increase with MAL + FRU + PEC + ALG ingestion (1.1 (SD 0.3) g·min; P = 1.0). No time-treatment interaction effects were observed for plasma glucose, lactate, insulin, or nonesterified fatty acids, or for ratings of perceived exertion or gastrointestinal symptoms (all, P > 0.05). CONCLUSION: To maximize exogenous carbohydrate oxidation during moderate-intensity running, athletes may benefit from consuming glucose(polymer)-fructose mixtures over glucose-based carbohydrates alone, but the addition of pectin and sodium alginate offers no further benefit.