Comparative analysis of short-chain fatty acid levels in non-alcoholic steatohepatitis rat model: Impact of high-fat high-fructose (HFHF), high fat, and Western diets.

The evidence on the role of diets in the production of short-chain fatty acids (SCFAs) was limited. The aim of this study was to assess the potential effects of high-fat high-fructose (HFHF), high-fat, and Western diets on the levels of SCFA. A research experiment employing a post-test-only control group design was carried out from January to April 2022. A total of 27 rats were randomly allocated to each study group. SCFA was measured two weeks after diet administration. Analysis of variance (ANOVA) test was used to analyze the differences among groups, and the effect estimate of each group was analyzed using post hoc Tukey. The concentrations of SCFAs post HFHF diets were recorded as follows: acetic acid at 54.60±10.58 mmol/g, propionic acid at 28.03±8.81 mmol/g, and butyric acid at 4.23±1.68 mmol/g. Following the high-fat diet, acetic acid measured 61.85±14.25 mmol/gr, propionic acid measured 25.19±5.55 mmol/gr, and butyric acid measured 6.10±2.93 mmol/gr. After the administration of Western diet, the levels of SCFA were 68.18±25.73, 29.69±12.76, and 7.48±5.51 mmol/g for acetic acid, propionic acid, and butyric acid, respectively. The level of butyric acid was significantly lower in HFHF diet group compared to the normal diet (mean difference (MD) 6.34; 95%CI: 0.61, 12.04; p=0.026). The levels of acetic acid (p=0.419) and propionic acid (p=0.316) were not statistically different among diet types (HFHF, high-fat, and Western diet). In conclusion, HFHF diet is associated with a lower level of butyric acid than the normal diet in a rat model.

Quercetin decreases fructose drinking in model of fructose-induced insulin resistance. Unexpected uric acid and TBARS lowering effect of methyl cellulose vehicle and fructose combination.

The aim of this study was to improve insulin sensitivity in fructose-treated animals by ingestion of flavonoid quercetin. Several signs of insulin resistance have been developed in rats by drinking 10% fructose solution for 9 weeks. The effect of 6-week-gavage-administrated quercetin (20 mg/kg/day in 1% methyl cellulose solution) was monitored. Rats of the control groups received methyl cellulose vehicle as well. The most striking result of the quercetin treatment was the normalization of the fructose solution drinking to the level of drinking water intake. In addition, quercetin supplementation considerably decreased the plasma glucose and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index in rats consuming fructose. Surprisingly, fructose ingestion did not elevate plasma uric acid, thiobarbituric acid reactive substances, nitrotyrosine, or advanced glycation end products fluorescence. Instead, a reduction of the above parameters was observed. In summary, these results indicate that quercetin supplementation reduces fructose drinking and decreases plasma glucose and the HOMA-IR index. Furthermore, methyl cellulose, in combination with fructose, causes uric acid - lowering, antioxidant and anti-glycation effects. Thus, methyl cellulose possibly shifts fructose metabolism in favor of the utilization of antioxidant features of fructose. Our results call for using methyl cellulose in sweetened beverages and other sweetened food.

Maternal fructose intake aggravates the harmful effects of a Western diet in rat male descendants impacting their cholesterol metabolism.

Scope: fructose consumption from added sugars correlates with the epidemic rise in MetS and CVD. Maternal fructose intake has been described to program metabolic diseases in progeny. However, consumption of fructose-containing beverages is allowed during gestation. Cholesterol is also a well-known risk factor for CVD. Therefore, it is essential to study Western diets which combine fructose and cholesterol and how maternal fructose can influence the response of progeny to these diets. Methods and results: a high-cholesterol (2%) diet combined with liquid fructose (10%), as a model of an unhealthy Western diet, was administered to descendants from control and fructose-fed mothers. Gene (mRNA and protein) expression and plasma, fecal and tissue parameters of cholesterol metabolism were measured. Interestingly, progeny from fructose-fed dams consumed less liquid fructose and cholesterol-rich chow than males from control mothers. Moreover, descendants of fructose-fed mothers fed a Western diet showed an increased cholesterol elimination through bile and feces than males from control mothers. Despite these mitigating circumstances to develop a proatherogenic profile, the same degree of hypercholesterolemia and severity of steatosis were observed in all descendants fed a Western diet, independently of maternal intake. An increased intestinal absorption of cholesterol, synthesis, esterification, and assembly into lipoprotein found in males from fructose-fed dams consuming a Western diet could be the cause. Moreover, an augmented GLP2 signalling seen in these animals would explain this enhanced lipid absorption. Conclusions: maternal fructose intake, through a fetal programming, makes a Western diet considerably more harmful in their descendants than in the offspring from control mothers.

Fenofibrate Improves Cognitive Impairment Induced by High-Fat High-Fructose Diet: A Possible Role of Irisin and Heat Shock Proteins.

A high-fat, high-fructose diet (HFFD) impairs cognitive functions and increases susceptibility to neurodegenerative disorders. Irisin and heat shock protein 70 (HSP70) are well known for their role in neuroprotection. The possible neuroprotective effects of fenofibrate on HFFD-induced cognitive dysfunction and the involvement of irisin and HSP70 in these effects were investigated in this study. Rats were divided into normal control, HFFD, dimethylsulfoxide+HFFD, and fenofibrate+HFFD groups. At the end of the experiment, fenofibrate treatment restored hippocampus histological characteristics to almost normal and improved HFFD-induced cognitive deficit. It reduced body weight gain and had hypolipidemic effects by significantly lowering total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol levels. It has antioxidant and anti-inflammatory effects as it significantly reduced the hippocampal malondialdehyde, interleukin-6, and tumor necrosis factor-alpha levels, while significantly increasing the reduced glutathione level. It prevented HFFD-induced hypoxia by significantly lowering hippocampal vascular endothelial growth factor and hypoxia-inducible factor-1 alpha levels. It significantly activated the hippocampal peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α)/irisin/brain-derived neurotrophic factor pathway. It significantly increased hippocampal HSP70 while decreasing the HSP90 levels. It enhanced synaptic plasticity by significantly upregulating the hippocampal relative GluR1 gene expression. Furthermore, hippocampal irisin levels in the HFFD group were found to be positively correlated with cognitive function, hippocampal HSP70, and relative GluR1 gene expression levels, while negatively correlated with hippocampal HSP90 and HIF1α levels. Therefore, fenofibrate may be used as a potential medication to treat HFFD-induced neurodegenerative disorders.

Efficacy of the Oral Administration of Maltodextrin Fructose Before Major Abdominal Surgery: A Prospective, Multicenter Clinical Study.

BACKGROUND: To study the efficacy of the oral administration of maltodextrin and fructose before major abdominal surgery (MAS). METHODS: This prospective, multicenter, parallel-controlled, double-blind study included patients aged 45-70 years who underwent elective gastrectomy, colorectal resection, or duodenopancreatectomy. The intervention group (IG) was given 800 mL and 400 mL of a maltodextrin and fructose beverage at 10 h and 2 h before MAS, respectively, and the control group (CG) received water under the same experimental conditions. The primary endpoint was insulin resistance index (IRI), and the secondary endpoints were fasting blood glucose, fasting insulin, insulin secretion index, insulin sensitivity index, intraoperative blood glucose, subjective comfort score, and clinical outcome indicators. RESULTS: A total of 240 cases were screened, of which 231 cases were randomly divided into two groups: 114 in the IG and 117 in the CG. No time-treatment effect was detected for any endpoint. The IRI and fasting insulin were significantly lower in the IG than CG after MAS (p = 0.02 & P = 0.03). The scores for anxiety, appetite, and nausea were significantly lower in the IG than CG at 1 h before MAS. Compared with baseline, the scores for appetite and nausea decreased in the IG but increased in the CG. CONCLUSION: The oral administration of maltodextrin and fructose before MAS can improve preoperative subjective well-being and reduce postoperative insulin resistance without increasing the risk of gastrointestinal discomfort.

Effects of Isocaloric Fructose Restriction on Ceramide Levels in Children with Obesity and Cardiometabolic Risk: Relation to Hepatic De Novo Lipogenesis and Insulin Sensitivity.

Sugar intake, particularly fructose, is implicated as a factor contributing to insulin resistance via hepatic de novo lipogenesis (DNL). A nine-day fructose reduction trial, controlling for other dietary factors and weight, in children with obesity and metabolic syndrome, decreased DNL and mitigated cardiometabolic risk (CMR) biomarkers. Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR. We evaluated the effect of fructose reduction on ceramides and correlations between changes observed and changes in traditional CMR biomarkers in this cohort. Analyses were completed on data from 43 participants. Mean weight decreased (-0.9 ± 1.1 kg). The majority of total and subspecies ceramide levels also decreased significantly, including dihydroceramides, deoxyceramides and ceramide-1-phoshates. Change in each primary ceramide species correlated negatively with composite insulin sensitivity index (CISI). Change in deoxyceramides positively correlated with change in DNL. These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR.

Preventive effects of black soybean polyphenols on non-alcoholic fatty liver disease in three different mouse models.

Non-alcoholic fatty liver disease (NAFLD) and its advanced stage, non-alcoholic steatohepatitis (NASH), are a major health issue throughout the world. Certain food components such as polyphenols are expected to possess preventive effects on NAFLD and NASH. In this study, the preventive effects of black soybean polyphenols were examined by using three NAFLD/NASH animal models. In a choline-deficient and L-amino acid-defined high-fat diet-induced NASH model, the intake of black soybean polyphenols decreased oxidative stress, but failed in attenuating liver injury and decreasing the expression of alpha-smooth muscle actin (α-SMA). In a Western diet with sucrose and fructose containing sweetened water-induced NAFLD model, black soybean polyphenols suppressed hepatic lipid accumulation, oxidative stress, aminotransferase activities in the plasma, inflammatory cytokine expression, and α-SMA expression accompanied by modulation of lipid metabolism. In a combination of Western diet and carbon tetrachloride model, black soybean polyphenols also suppressed hepatic lipid accumulation, oxidative stress, aminotransferase activities in the plasma, and α-SMA expression. In conclusion, black soybean is an attractive food for the prevention of NAFLD and NASH due to its strong antioxidant activity.

Fructose ingestion modifies NMDA receptors and exacerbates the seizures induced by kainic acid.

Fructose ingestion elicits a diversity of brain alterations, but it is unknown how it affects N-methyl-D-Aspartate receptors (NMDAr). Here, we analyzed the expression of NMDAr subunits and protein kinases after the long-term dietary fructose intake. Since NMDAr are related to epileptogenesis, we also examined whether fructose increases the susceptibility to seizures after the microinjection of kainic acid (KA) in the rat hippocampus. Wistar rats were randomly divided into water (control) and fructose groups. For twelve weeks, groups had ad libitum access to water or fructose solution (10% w/v). After treatment, hippocampal protein expression of NMDAr subunits and protein kinases involved in NMDAr regulation were analyzed. Additionally, electroencephalographic and behavioral changes related to seizures were evaluated after the microinjection of a sub-convulsive dose of KA in the hippocampus. Fructose induced the decrease of NR1 and, conversely, the increase of NR2A subunits expression in the hippocampus. Also, the phosphorylation of protein kinase C alpha (PKCα) and c-Src increased significantly. No electroencephalographic or behavioral patterns related to convulsive motor seizures were observed in the control group. However, all the rats that ingested fructose showed stage 3 seizures (forelimb clonus) and a significant increase in the number of wet-dog shakes. Moreover, electroencephalographic recordings revealed pronounced epileptiform activity and increased total spectral power at 30 and 60 min after the microinjection of KA. This study shows for the first time that fructose intake exacerbates the seizures induced by KA. Therefore, we propose that this proconvulsant effect could be mediated by changes in NMDAr subunits expression and increased activation of kinases modulating NMDAr function.

High fructose diet-induced obesity worsens post-ischemic brain injury in the hippocampus of female rats.

Objectives: Cerebral ischemia is caused by a reduction of the blood flow in a specific area in the brain, triggering cellular cascades in the tissue that result in neuronal death. This phenomenon leads to neurological decline in patients with stroke. The extent of the injury after stroke could be related to the condition of obesity. Thus, we aim to analyze the effect of obesity induced by a high fructose diet (HFD) on the brain after cerebral ischemia in rats.Methods: We induced the obesity model in female Wistar rats with 20% fructose in water for 11 weeks. We then performed cerebral ischemia surgery (2-vessel occlusion), carried out the neurological test 6, 24 and 48 h post-ischemia and analyzed the histological markers.Results: The HFD induced an obese phenotype without insulin resistance. The obese rats exhibited worse neurological performance at 6 h post-ischemia and showed neuronal loss and astroglial and microglial immunoreactivity changes in the caudate putamen, motor cortex, amygdala and hippocampus at 48 h post-ischemia. However, the most commonly affected area was the hippocampus, where we found an increase in interleukin 1ß in the blood vessels of the dentate gyrus, a remarkable disruption of MAP-2+ dendrites, a loss of brain-derived neurotrophic factor and the presence of PHF-tau. In conclusion, a HFD induces an obese phenotype and worsens the neuronal loss, inflammation and plasticity impairment in the hippocampus after cerebral ischemia.

Acute and chronic metabolic effects of carvedilol in high-fructose, high-fat diet-fed mice: implication of ß-arrestin2 pathway.

We aimed to investigate the acute and chronic effects of carvedilol on insulin resistance in high-fructose, high-fat diet (HFrHFD) - fed mice and the implication of the ß-arrestin2 pathway. The acute effect of carvedilol (10 mg/kg, i.p.) on glucose tolerance and hepatic lipid signaling in normal and insulin resistant mice was investigated. Then, the chronic effect of carvedilol on insulin resistance and dyslipidemia in HFrHFD-fed mice was examined. Changes in ß-arrestin2 and its downstream signals in liver, skeletal muscle, and adipose tissue were measured. This involved measuring phosphatidylinositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) levels and protein kinase B (AKT) activity. Carvedilol acutely reduced fasting blood glucose levels in both normal and insulin resistant mice without significantly affecting the glucose tolerance. These acute effects were associated with increased hepatic PIP2 but decreased hepatic DAG levels. Chronic administration of carvedilol significantly ameliorated insulin resistance and dyslipidemia in HFrHFD-fed mice. These chronic effects were associated with increased ß-arrestin2, PIP2, and AKT activity levels but decreased DAG levels in the classical insulin target tissues. In conclusion, carvedilol acutely maintains glucose homeostasis and chronically ameliorates insulin resistance and dyslipidemia in HFrHFD-fed mice. The insulin sensitizing effects of carvedilol are highly correlated with the upregulation of ß-arrestin2 pathway.

Glucose and Fructose Hydrogel Enhances Running Performance, Exogenous Carbohydrate Oxidation, and Gastrointestinal Tolerance.

PURPOSE: Beneficial effects of carbohydrate (CHO) ingestion on exogenous CHO oxidation and endurance performance require a well-functioning gastrointestinal (GI) tract. However, GI complaints are common during endurance running. This study investigated the effect of a CHO solution-containing sodium alginate and pectin (hydrogel) on endurance running performance, exogenous and endogenous CHO oxidation, and GI symptoms. METHODS: Eleven trained male runners, using a randomized, double-blind design, completed three 120-min steady-state runs at 68% V˙O2max, followed by a 5-km time-trial. Participants ingested 90 g·h-1 of 2:1 glucose-fructose (13C enriched) as a CHO hydrogel, a standard CHO solution (nonhydrogel), or a CHO-free placebo during the 120 min. Fat oxidation, total and exogenous CHO oxidation, plasma glucose oxidation, and endogenous glucose oxidation from liver and muscle glycogen were calculated using indirect calorimetry and isotope ratio mass spectrometry. GI symptoms were recorded throughout the trial. RESULTS: Time-trial performance was 7.6% and 5.6% faster after hydrogel ([min:s] 19:29 ± 2:24, P < 0.001) and nonhydrogel (19:54 ± 2:23, P = 0.002), respectively, versus placebo (21:05 ± 2:34). Time-trial performance after hydrogel was 2.1% faster (P = 0.033) than nonhydrogel. Absolute and relative exogenous CHO oxidation was greater with hydrogel (68.6 ± 10.8 g, 31.9% ± 2.7%; P = 0.01) versus nonhydrogel (63.4 ± 8.1 g, 29.3% ± 2.0%; P = 0.003). Absolute and relative endogenous CHO oxidation was lower in both CHO conditions compared with placebo (P < 0.001), with no difference between CHO conditions. Absolute and relative liver glucose oxidation and muscle glycogen oxidation were not different between CHO conditions. Total GI symptoms were not different between hydrogel and placebo, but GI symptoms were higher in nonhydrogel compared with placebo and hydrogel (P < 0.001). CONCLUSION: The ingestion of glucose and fructose in hydrogel form during running benefited endurance performance, exogenous CHO oxidation, and GI symptoms compared with a standard CHO solution.

High-Fructose, High-Fat Diet Alters Muscle Composition and Fuel Utilization in a Juvenile Iberian Pig Model of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a serious metabolic condition affecting millions of people worldwide. A "Western-style diet" has been shown to induce pediatric NAFLD with the potential disruption of skeletal muscle composition and metabolism. To determine the in vivo effect of a "Western-style diet" on pediatric skeletal muscle fiber type and fuel utilization, 28 juvenile Iberian pigs were fed either a control diet (CON) or a high-fructose, high-fat diet (HFF), with or without probiotic supplementation, for 10 weeks. The HFF diets increased the total triacylglycerol content of muscle tissue but decreased intramyocellular lipid (IMCL) content and the number of type I (slow oxidative) muscle fibers. HFF diets induced autophagy as assessed by LC3I and LC3II, and inflammation, as assessed by IL-1α. No differences in body composition were observed, and there was no change in insulin sensitivity, but HFF diets increased several plasma acylcarnitines and decreased expression of lipid oxidation regulators PGC1α and CPT1, suggesting disruption of skeletal muscle metabolism. Our results show that an HFF diet fed to juvenile Iberian pigs produces a less oxidative skeletal muscle phenotype, similar to a detraining effect, and reduces the capacity to use lipid as fuel, even in the absence of insulin resistance and obesity.

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.

Maternal fructose intake predisposes rat offspring to metabolic disorders via abnormal hepatic programming.

Given that fructose consumption has increased by more than 10-fold in recent decades, it is possible that excess maternal fructose consumption causes harmful effects in the next generation. This study attempted to elucidate the mechanism of the harmful effects of excessive maternal fructose intake from the perspective of offspring liver function. Female rats during gestation and lactation were fed water containing fructose, and their offspring were fed normal water. We attempted to elucidate the mechanism of fructose-induced transgenerational toxicity by conducting a longitudinal study focusing on hepatic programming prior to disease onset. Impaired Insulin resistance and decreased high-density lipoprotein-cholesterol levels were observed at 160 days of age. However, metabolic disorders were not observed in 60-day-old offspring. Microarray analysis of 60-day-old offspring livers showed the reduction of hepatic insulin-like growth factor-1 (Igf1) mRNA expression. This reduction continued until the rats were aged 160 days and attenuated Igf1 signaling. Hepatic microRNA-29 (miR-29a) and miR-130a, which target Igf1 mRNA, were also found to be upregulated. Interestingly, these miRNAs were upregulated in the absence of metabolic disorder. In this study, we found that maternal fructose intake resulted in dysregulated expression of Igf1 and its target miRNAs in the offspring liver, and that these offspring were more likely to develop metabolic disorders. Abnormal hepatic programming induced by an imbalanced maternal nutritional environment is maintained throughout life, implying that it may contribute to metabolic disorders.

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.

Maternal high fructose diet exacerbates white adipose tissue thermogenic process in offspring upon exposure to cold temperature.

AIM: An adverse endogenous environment during early life predisposes to metabolic disorder development. We previously reported adverse metabolic and adipose tissue effects in adult male rats born to dams fed with a fructose-rich diet (FRD). The aim of this work was to determine the effect of a FRD consumed by the pregnant mother on the white adipose tissue (WAT) browning capacity of male offspring at adulthood. MAIN METHODS: Adult SD male offspring from control (C) and FRD-fed mothers were exposed during one week to a cold stimulus. WAT browning capacity was studied through in vivo and in vitro approaches. KEY FINDINGS: After cold exposure, WAT browning was higher in fructose-programmed animals as evidenced by an increase in ucp-1 gene expression, protein levels, and higher UCP-1 positive foci. Moreover, pgc1-α gene expression was increased. In vitro studies showed a lower adipogenic capacity in cells of prenatally fructose-exposed animals differentiated with a white differentiation cocktail, while a higher ucp-1 expression was noted when their cells were treated with a pro-beige differentiation cocktail. SIGNIFICANCE: For the first time we demonstrate that pre-natal fructose exposure predisposes programmed male rats to a higher WAT browning-induced response, under stimulated conditions, despite an apparent lower basal thermogenic capacity. These results should be considered in future studies to generate new therapeutic approaches to deal with adverse programming malnutrition effects.

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.