Soft drink consumption has become a highly controversial public health issue. Given the pattern of consumption in China, sugar-sweetened beverage is the main type of soft drink consumed. Due to containing high levels of fructose, a soft drink may have a deleterious effect on handgrip strength (HGS) due to oxidative stress, inflammation and insulin resistance. However, few studies show an association between soft drink consumption and HGS in adults. We aimed to investigate the association between soft drink consumption and longitudinal changes in HGS among a Chinese adult population. A longitudinal population-based cohort study (5-year follow-up, median: 3·66 years) was conducted in Tianjin, China. A total of 11 125 participants (56·7 % men) were enrolled. HGS was measured using a handheld digital dynamometer. Soft drink consumption (mainly sugar-containing carbonated beverages) was measured at baseline using a validated FFQ. ANCOVA was used to evaluate the association between soft drink consumption and annual change in HGS or weight-adjusted HGS. After adjusting for multiple confounding factors, the least square means (95 % CI) of annual change in HGS across soft drink consumption frequencies were −0·70 (–2·49, 1·09) for rarely drinks, −0·82 (–2·62, 0·97) for < 1 cup/week and −0·86 (–2·66, 0·93) for ≥ 1 cup/week (Pfor trend < 0·05). Likewise, a similar association was observed between soft drink consumption and annual change in weight-adjusted HGS. The results indicate that higher soft drink consumption was associated with faster HGS decline in Chinese adults.

Fructose (C6H12O6) is acutely obesogenic and is a risk factor for hypertension, cardiovascular disease, and nonalcoholic fatty liver disease. However, the possible long-lasting effects of early-life fructose consumption have not been studied. We tested for effects of early-life fructose and/or wheel access (voluntary exercise) in a line of selectively bred High Runner (HR) mice and a non-selected Control (C) line. Exposures began at weaning and continued for 3 weeks to sexual maturity, followed by a 23-week "washout" period (equivalent to ∼17 human years). Fructose increased total caloric intake, body mass, and body fat during juvenile exposure, but had no effect on juvenile wheel running and no important lasting effects on adult physical activity or body weight/composition. Interestingly, adult maximal aerobic capacity (VO2max) was reduced in mice that had early-life fructose and wheel access. Consistent with previous studies, early-life exercise promoted adult wheel running. In a 3-way interaction, C mice that had early-life fructose and no wheel access gained body mass in response to 2 weeks of adult wheel access, while all other groups lost mass. Overall, we found some long-lasting positive effects of early-life exercise, but minimal effects of early-life fructose, regardless of the mouse line.

The purpose of the study was to verify the effect of 4 weeks of a high-fructose diet (HFD) associated with aerobic training on the risk factors for cardiometabolic diseases. Twenty-one young adults were randomised into three groups: HFD (HFD: 1 g/kg body weight of fructose/day), high-glucose diet (HGD: 1 g/kg body weight of glucose/day) and high-fructose diet and exercise (HFDE: 1 g/kg body weight of fructose/day + 3 weekly 60-minute sessions of aerobic exercise). Before and after the 4 weeks of the intervention, blood samples were taken and flow-mediated dilatation, insulin resistance index, pancreatic beta cell functional capacity index, insulin sensitivity index and 24-h blood pressure were evaluated. HFD showed an increase in uric acid concentrations (P = 0·040), and HGD and HFDE groups showed no changes in this outcome between pre- and post-intervention; however, the HFDE group showed increased uric acid concentrations from the middle to the end of the intervention (P = 0·013). In addition, the HFD group showed increases in nocturnal systolic blood pressure (SBP) (P = 0·022) and nocturnal diastolic blood pressure (DBP) (P = 0·009). The HGD group exhibited decreases in nocturnal SBP (P = 0·028) and nocturnal DBP (P = 0·031), and the HFDE group showed a decrease in 24-h SBP (P = 0·018). The consumption of 1 g/kg of fructose per day may increase uric acid concentrations and blood pressure in adults. Additionally, aerobic exercises along with fructose consumption attenuate changes in uric acid concentrations and prevent impairment in nocturnal blood pressure.

Fructose (C6H12O6), also known as levulose, is a hexose. Chronic consumption of fructose may be associated with increased intrahepatic fat concentration and the development of insulin resistance as well as an increase in the prevalence of nonalcoholic fatty liver disease and hyperlipidemia during pregnancy. Despite the existence of many studies regarding the consumption of fructose in pregnancy, its effects on fetuses have not yet been fully elucidated. Therefore, the objective of this study was to evaluate the genetic and biochemical effects in offspring (male and female) of female mice treated with fructose during pregnancy and lactation. Pairs of 60-day-old Swiss mice were used and divided into three groups; negative control and fructose, 10%/l and 20%/l doses of fructose groups. After offspring birth, the animals were divided into six groups: P1 and P2 (males and females), water; P3 and P4 (males and females) fructose 10%/l; and P5 and P6 (males and females) fructose 20%/l. At 30 days of age, the animals were euthanized for genetic and biochemical assessments. Female and male offspring from both dosage groups demonstrated genotoxicity (evaluated through comet assay) and oxidative stress (evaluated through nitrite concentration, sulfhydril content and superoxide dismutase activity) in peripheral and brain tissues. In addition, they showed nutritional and metabolic changes due to the increase in food consumption, hyperglycemia, hyperlipidemia, and metabolic syndrome. Therefore, it is suggested that high consumption of fructose by pregnant female is harmful to their offspring. Thus, it is important to carry out further studies and make pregnant women aware of excessive fructose consumption during this period.

There are few data on the effects on TAG, glucose and uric acid of chronic consumption of a moderate dose of fructose in solid foods. Twenty-eight participants with prediabetes and/or obesity and overweight commenced the study (BMI 32·3 kg/m2, age 44·7 years, fasting glucose 5·3 (sd 0·89) mmol/l and 2-h glucose 6·6 (sd 1·8) mmol/l). Twenty-four men and women who completed the study consumed, in random order, two acute test meals of muffins sweetened with either fructose or sucrose. This was followed by 4-week chronic consumption of 42 g/d of either fructose or sucrose in low-fat muffins after which the two meal tests were repeated. The sugar type in the chronic feeding period was also randomised. Fasting TAG increased after chronic consumption of fructose by 0·31 (sd 0·37) mmol/l compared with sucrose in those participants with impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (P = 0·004). Total cholesterol (0·33 mmol/l), LDL-cholesterol (0·24 mmol/l) and HDL-cholesterol (0·08 mmol/l) increased significantly over the 1- month feeding period with no differences between muffin types. Fasting glucose was not different after 1 month of muffin consumption. Uric acid response was not different between the two sugar types either baseline or 1 month, and there were no differences between baseline and 1 month. The increase in fasting TAG in participants with IFG/IGT suggests the need for caution in people at increased risk of type 2 diabetes.

Experimental studies have demonstrated the effects of maternal fructose consumption during pregnancy and lactation on metabolic alterations in their offspring, especially male offspring. However, few studies have focused on female offspring after providing fructose in food to dam rats. Here, we studied whether offspring of both sexes were differentially affected by a maternal high-fructose diet (HFD). For this purpose, Sprague-Dawley rats were fed during pregnancy and lactation with a standard diet (SD) or a HFD (50% w/w). After weaning, offspring were fed an SD; 3 days later, dams were sacrificed, and their offspring were sacrificed on postnatal day 90. Body weight (BW), food and water intake (only for dams), and various biomarkers of metabolic syndrome were measured. When compared to the SD-fed dams, HFD-fed dams had a reduction in BW and food and water intake. Conversely, adiposity, liver weight, liver lipids, and plasma levels of glucose, insulin, cholesterol, triglycerides, and uric acid were increased in HFD-fed dams. Moreover, the BW, food consumption, weight of retroperitoneal fat pads, and liver lipids increased in female and male offspring of HFD-fed dams. Interestingly, the pups of HFD-fed mothers showed increased levels of leptin and insulin resistance and decreased levels of adiponectin which were more pronounced in male offspring than in female offspring. In contrast, a higher increase in BW was shown earlier in female offspring. Thus, high-fructose consumption by dams during pregnancy and lactation led to sex-specific developmental programming of the metabolic syndrome phenotype in adult offspring.

During the early postnatal period, dietary manipulations can alter the developmental trajectory of the growing offspring, causing beneficial or adverse health outcomes later in adult life. We investigated the potential preventive effects of neonatal zingerone intake on the development of fructose-induced metabolic derangements in rats.

Four-day old male and female Sprague-Dawley rat pups (n = 79) were randomly grouped and administered: 10 ml/kg body weight (bwt) of distilled water (W), 10 ml/kg bwt 20% fructose solution (FS), 10 ml/kg bwt fructose solution + 40 mg/kg bwt of zingerone in distilled water (ZF) or 40 mg/kg bwt of zingerone in distilled water (ZW) pre-weaning. After weaning, W and ZW continued on unlimited tap water, while FS and ZF continued on unlimited fructose solution for 10 weeks. Body mass and food and fluid intake were evaluated, plasma was collected for metabolic assays and visceral fat was quantified.

Food intake was decreased, fructose and overall caloric intake were increased due to fructose feeding in both sexes (P < 0.05). When compared with the controls, the high-fructose diet significantly raised the terminal body masses of females (P < 0.0001), concentrations of triglycerides, total cholesterol, LDL-c, TG:HDL-c ratio and visceral fat mass relative to bwt in both sexes (P < 0.05). Zingerone prevented (P < 0.05) the fructose-induced increase in body mass (females) and hypercholesterolemia (both sexes). Levels of HDL-c, glycaemic parameters and adiponectin were not affected by the interventions (P > 0.05). Sex-related differences were observed in food, fluid and caloric intake, terminal mass, cholesterol subtypes and visceral fat percentage (P < 0.05).

Zingerone could be used strategically in the neonatal phase as a prophylatic management of high-fructose diet-induced metabolic syndrome.

Overconsumption of fructose time dependently induces the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether ursolic acid (UA) intake by new-born rats would protect against fructose-induced NAFLD. One hundred and seven male and female Sprague Dawley rat pups were randomly grouped and gavaged (10 ml/kg body weight) with either 0.5% dimethylsulphoxide (vehicle control), 0.05% UA, 50% fructose mixed with UA (0.05%) or 50% fructose alone, from postnatal day 6 (P6) to P20. Post-weaning (P21–P69), the rats received normal rat chow (NRC) and water to drink. On P70, the rats in each group were continued on water or 20% fructose to drink, as a secondary high fructose diet during adulthood. After 8 weeks, body mass, food and fluid intake, circulating metabolites, visceral adiposity, surrogate markers of liver function and indices of NAFLD were determined. Food intake was reduced as a result of fructose feeding in both male and female rats (p < 0.0001). Fructose consumption in adulthood significantly increased fluid intake and visceral adiposity in female rats (p < 0.05) and had no apparent effects in male rats (p > 0.05). In both sexes of rats, fructose had no significant (p > 0.05) effects on body mass, circulating metabolites, total calorie intake and surrogate markers of hepatic function. Fructose consumption in both early life and adulthood in female rats promoted hepatic lipid accumulation (p < 0.001), hypertrophy, microvesicular and macrovesicular steatosis (p < 0.05). Early-life UA intake significantly (p < 0.001) reduced fructose-induced hepatic lipid accumulation in both male and female rats. Administration of UA during periods of developmental plasticity shows prophylactic potential against dietary fructose-induced NAFLD.

In ruminant diets, soluble sugar is an important factor in the digestive process. The objective of this study was to evaluate the effects of the source and dose of soluble sugars, under controlled pH conditions, on the in vitro digestibility of DM, fibre fractions (NDF and ADF) and cell wall neutral monosaccharides of corn silage. Silage was collected from several points in a silage mass from a bunker silo, oven-dried at 55°C and ground through a 1-mm screen. Sub-samples were combined with sugars to compose the treatments, in a 5 × 5 factorial arrangement, as a combination of five soluble sugar sources (glucose, fructose, arabinose, xylose and sucrose) and five sugar doses (0, 100, 200, 300 and 400 g/kg sugar in DM corn silage), respecting the following proportions of sugar : corn silage, 0 : 100, 10 : 90, 20 : 80, 30 : 70, 40 : 60 represented by the sugar doses, respectively. An in vitro test was performed to determine the true digestibility (D) of the chemical entities (DM, NDF and ADF) and cell wall monosaccharides (glucose = gluc, arabinose = arab and xylose = xyl). During the first 12 h of incubation, the pH was maintained above 6.0 by the addition of 2.5 N NaOH. The concentrations of neutral monosaccharides (arabinose, xylose and glucose) were determined by GLC. The soluble sugars decreased the digestibility of corn silage followed by pH reduction, especially at doses higher than 200 g/kg sugar. Overall, xylose, followed by sucrose, fructose and arabinose, had greater impacts on DM digestibility, whereas fibre digestibility was impaired by sucrose at all doses. Xylose and fructose had greater impacts on NDF digestibility at 300 and 400 g/kg sugar. Although xylose impaired the Dgluc in the cell wall in all doses. All doses of glucose improved the Dgluc and Dxyl in the cell wall.

Irritable bowel syndrome (IBS) is a chronic disorder characterised by recurrent abdominal pain or discomfort and transit disturbances with heterogeneous pathophysiological mechanisms. The link between food and gastrointestinal (GI) symptoms is often reported by patients with IBS and the role of fructose has recently been highlighted. Fructose malabsorption can easily be assessed by hydrogen and/or methane breath test in response to 25 g fructose; and its prevalence is about 22 % in patients with IBS. The mechanism of fructose-related symptoms is incompletely understood. Osmotic load, fermentation and visceral hypersensitivity are likely to participate in GI symptoms in the IBS population and may be triggered or worsened by fructose. A low-fructose diet could be integrated in the overall treatment strategy, but its role and implication in the improvement of IBS symptoms should be evaluated. In the present review, we discuss fructose malabsorption in adult patients with IBS and the interest of a low-fructose diet in order to underline the important role of fructose in IBS.

Studies on the intake of different types of carbohydrates and long-term mortality are sparse. We examined the association of starch, total and each type of sugar and free sugars with the risk of total and cause-specific mortality in a cohort of the general population in Japan. Study subjects were 29 079 residents from the Takayama Study, Japan, who responded to a self-administered questionnaire in 1992. Diet was assessed by a validated FFQ at the baseline. Mortality was ascertained during 16 years of follow-up. We noted 2901 deaths (974 cancer related and 775 cardiovascular related) in men and 2438 death (646 cancer related and 903 cardiovascular related) in women. In men, intake of starch was inversely associated with total mortality after controlling for covariates (hazard ratio (HR) for the highest quartile v. lowest quartile: 0·71; 95 % CI 0·60, 0·84; Ptrend < 0·001). Intakes of total sugars, glucose, fructose, sucrose, maltose and free and naturally occurring sugars were significantly positively associated with total mortality in men (HR for the highest v. lowest quartile of total sugar: 1·27; 95 % CI 1·12, 1·45; Ptrend < 0·0001). Similar relations were observed for cardiovascular mortality and non-cancer, non-cardiovascular mortality in men. In women, there was no significant association between any type of carbohydrates and mortality except that intake of free sugars was significantly positively associated with total and non-cancer, non-cardiovascular mortality. Data suggest that the high intake of starch reduces mortality, whereas the high intake of sugars, including glucose, fructose and sucrose, increases mortality in Japanese men.

For decades, fructose intake has been recognised as an environmental risk for metabolic syndromes and diseases. Here we comprehensively examined the effects of fructose intake on mice liver transcriptomes. Fructose-supplemented water (34 %; w/v) was fed to both male and female C57BL/6N mice at their free will for 6 weeks, followed by hepatic transcriptomics analysis. Based on our criteria, differentially expressed genes (DEG) were selected and subjected to further computational analyses to predict key pathways and upstream regulator(s). Subsequently, predicted genes and pathways from the transcriptomics dataset were validated via quantitative RT-PCR analyses. As a result, we identified eighty-nine down-regulated and eighty-eight up-regulated mRNA in fructose-fed mice livers. These DEG were subjected to bioinformatics analysis tools in which DEG were mainly enriched in xenobiotic metabolic processes; further, in the Ingenuity Pathway Analysis software, it was suggested that the aryl hydrocarbon receptor (AhR) is an upstream regulator governing overall changes, while fructose suppresses the AhR signalling pathway. In our quantitative RT-PCR validation, we confirmed that fructose suppressed AhR signalling through modulating expressions of transcription factor (AhR nuclear translocator; Arnt) and upstream regulators (Ncor2, and Rb1). Altogether, we demonstrated that ad libitum fructose intake suppresses the canonical AhR signalling pathway in C57BL/6N mice liver. Based on our current observations, further studies are warranted, especially with regard to the effects of co-exposure to fructose on (1) other types of carcinogens and (2) inflammation-inducing agents (or even diets such as a high-fat diet), to find implications of fructose-induced AhR suppression.

The present paper reviews the physiological responses of human liver carbohydrate metabolism to physical activity and ingestion of dietary sugars. The liver represents a central link in human carbohydrate metabolism and a mechanistic crux point for the effects of dietary sugars on athletic performance and metabolic health. As a corollary, knowledge regarding physiological responses to sugar ingestion has potential application to either improve endurance performance in athletes, or target metabolic diseases in people who are overweight, obese and/or sedentary. For example, exercise increases whole-body glycogen utilisation, and the breakdown of liver glycogen to maintain blood glucose concentrations becomes increasingly important as exercise intensity increases. Accordingly, prolonged exercise at moderate-to-high exercise intensity results in depletion of liver glycogen stores unless carbohydrate is ingested during exercise. The exercise-induced glycogen deficit can increase insulin sensitivity and blood glucose control, and may result in less hepatic lipid synthesis. Therefore, the induction and maintenance of a glycogen deficit with exercise could be a specific target to improve metabolic health and could be achieved by carbohydrate (sugar) restriction before, during and/or after exercise. Conversely, for athletes, maintaining and restoring these glycogen stores is a priority when competing in events requiring repeated exertion with limited recovery. With this in mind, evidence consistently demonstrates that fructose-containing sugars accelerate post-exercise liver glycogen repletion and could reduce recovery time by as much as half that seen with ingestion of glucose (polymers)-only. Therefore, athletes aiming for rapid recovery in multi-stage events should consider ingesting fructose-containing sugars to accelerate recovery.

The aim of this study was to re-examine the chronic effect (>7 d) of fructose consumption on postprandial TAG, in adolescents and adults. The research was carried out in March 2017 and used different electronic databases, such as Medline® (Pubmed®), Embase® and Cochrane. The review considered clinical trials (parallel or crossed) that evaluated the effect of fructose consumption for a period longer than 7 d, in humans. Two investigators independently performed data extraction. The outcome was the absolute delta of TAG concentration in a 4-h postprandial period. The results were presented with delta mean difference between treatments with 95 % CI. The calculations were made based on random-effect models. Statistical heterogeneity of treatment effects between studies was assessed by Cochrane’s ‘Q Test’ and ‘I2’ inconsistency test. The meta-analysis of the twelve selected interventions (n 318) showed that fructose generated larger variation (δ) of TAG concentrations during the postprandial period, compared with other carbohydrates (mean difference: 8·02 (95 % CI 0·46, 15·58) mg/dl (0·09 (95 % CI 0·01, 0·18) mmol/l); I2: 74 %). High heterogeneity was generated almost exclusively by one study, and its withdrawal did not alter the result. We concluded that chronic consumption of fructose (>7 d) has a negative role on postprandial TAG in healthy adolescents and adults, as well as in overweight/obese individuals, but not in diabetics.

Dietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated the potential hepatoprotective effects of neonatal administration of oleanolic acid (OA), a phytochemical, on the subsequent development in adulthood, of dietary fructose-induced NAFLD. Male and female suckling rats (n=112) were gavaged with; distilled water (DW), OA (60 mg/kg), high fructose solution (HF; 20% w/v) and OA+HF (OAHF) for 7 days. The rats were weaned onto normal rat chow on day 21 up to day 55. From day 56, half of the rats in each treatment group were continued on plain water or HF as drinking fluid for 8 weeks. Hepatic lipid accumulation and hepatic histomorphometry were then determined. Fructose consumption in adulthood following neonatal fructose intake (HF+F) caused a 47–49% increase in hepatic lipid content of both male and female rats (P<0.05). However, fructose administered in adulthood only, caused a significant increase (P<0.05) in liver lipid content in females only. NAFLD activity scores for inflammation and steatosis were higher in the fructose-fed rats compared with other groups (P<0.05). Steatosis, low-grade inflammation and fibrosis were observed in rats that received HF+F. NAFLD area fraction for fibrosis was three times higher in rats that received fructose neonatally and in adulthood compared with the rats in the negative control group (P<0.05). Treatment with OA during a critical window of developmental plasticity in rats prevented the development of fructose-induced NAFLD.

Endothelial function is a key mechanism in the development of CVD. Arginine and exercise are important non-pharmacological strategies for mitigating the impact of metabolic changes in the metabolic syndrome, but the effect of their combined administration is unknown. Thus, the aim of this study was to investigate the isolated and combined effects of aerobic training and arginine supplementation on metabolic variables and vascular reactivity in rats at high risk for developing the metabolic syndrome. Wistar rats were divided into two groups: control and fructose (F – water with 10 % fructose). After 2 weeks, the F group was divided into four groups: F, fructose+arginine (FA, 880 mg/kg per d of l-arginine), fructose+training (FT) and fructose+arginine+training (FTA); treatments lasted for 8 weeks, and no difference was observed in body mass gain. Arginine did not improve the body protein content, and both the FA and FT groups show a reversal of the increase in adipose tissue. Insulin increase was prevented by training and arginine, without additive effect, and the increase in serum TAG was prevented only by training. The F group showed impaired endothelium-dependent vasodilation and hyperreactivity to phenylephrine, but arginine and training were capable of preventing these effects, even separately. Higher nitric oxide level was observed in the FA and FT groups, and no potentiating effect was detected. Thus, only training was able to prevent the increase in TAG and improve the protein mass, and training and arginine exert similar effects on fat content, insulin and endothelial function, but these effects are not additive.

Metabolic syndrome is linked to the consumption of fructose-rich diets. Nutritional and pharmacological interventions perinatally can cause epigenetic changes that programme an individual to predispose or protect them from the development of metabolic diseases later. Hibiscus sabdariffa (HS) reportedly has anti-obesity and hypocholesterolaemic properties in adults. We investigated the impact of neonatal intake of HS on the programming of metabolism by fructose. A total of 85 4-day-old Sprague Dawley rats were divided randomly into three groups. The control group (n=27, 12 males, 15 females) received distilled water at 10 ml/kg body weight. The other groups received either 50 mg/kg (n=30, 13 males, 17 females) or 500 mg/kg (n=28, 11 males, 17 females) of an HS aqueous calyx extract orally till postnatal day (PND) 14. There was no intervention from PND 14 to PND 21 when the pups were weaned. The rats in each group were then divided into two groups; one continued on a normal diet and the other received fructose (20% w/v) in their drinking water for 30 days. The female rats that were administered with HS aqueous calyx extract as neonates were protected against fructose-induced hypertriglyceridaemia and increased liver lipid deposition. The early administration of HS resulted in a significant (P⩽0.05) increase in plasma cholesterol concentrations with or without a secondary fructose insult. In males, HS prevented the development of fructose-induced hypercholesterolaemia. The potential beneficial and detrimental effects of neonatal HS administration on the programming of metabolism in rats need to be considered in the long-term well-being of children.

Steatosis can sensitise the liver to various challenges and favour the development of non-alcoholic fatty liver disease (NAFLD). In this context, fructose feeding promotes endotoxin translocation from the gut, contributing to disease progression via an inflammatory process. Citrulline is protective against fructose-induced NAFLD; we hypothesised that this property might be related to its anti-inflammatory and antioxidative action against endotoxin-induced hepatic injuries. This hypothesis was evaluated in a model of perfused liver isolated from NAFLD rats. Male Sprague–Dawley rats (n 30) were fed either a standard rodent chow or a 60 % fructose diet alone, or supplemented with citrulline (1 g/kg per d) for 4 weeks. After an evaluation of their metabolic status, fasted rats received an intraperitoneal injection of lipopolysaccharide (LPS) (2·5 mg/kg). After 1 h, the livers were isolated and perfused for 1 h to study liver function and metabolism, inflammation and oxidative status. In vivo, citrulline significantly decreased dyslipidaemia induced by a high-fructose diet and insulin resistance. In the isolated perfused rat livers, endotoxaemia resulted in higher cytolysis (alanine aminotransferase release) and higher inflammation (Toll-like receptor 4) in livers of fructose-fed rats, and it was prevented by citrulline supplementation. Oxidative stress and antioxidative defences were similar in all three groups. Amino acid exchanges and metabolism (ammonia and urea release) were only slightly different between the three groups. In this context of mild steatosis, our results suggest that fructose-induced NAFLD leads to an increased hepatic sensitivity to LPS-induced inflammation. Citrulline-induced restriction of the inflammatory process may thus contribute to the prevention of NAFLD.