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The presence of obesity and metabolic syndrome is strongly linked with chronic kidney disease (CKD), but the mechanisms responsible for the association are poorly understood. Here, we tested the hypothesis that mice with obesity and metabolic syndrome might have increased susceptibility to CKD from liquid high fructose corn syrup (HFCS) by favoring the absorption and utilization of fructose. We evaluated the pound mouse model of metabolic syndrome to determine if it showed baseline differences in fructose transport and metabolism and whether it was more susceptible to chronic kidney disease when administered HFCS. Pound mice have increased expression of fructose transporter (Glut5) and fructokinase (the limiting enzyme driving fructose metabolism) associated with enhanced fructose absorption. Pound mice receiving HFCS rapidly develop CKD with increased mortality rates associated with intrarenal mitochondria loss and oxidative stress. In pound mice lacking fructokinase, the effect of HFCS to cause CKD and early mortality was aborted, associated with reductions in oxidative stress and fewer mitochondria loss. Obesity and metabolic syndrome show increased susceptibility to fructose-containing sugars and increased risk for CKD and mortality. Lowering added sugar intake may be beneficial in reducing the risk for CKD in subjects with metabolic syndrome.

Sugar consumption can readily lead to obesity and metabolic diseases such as liver steatosis. We previously demonstrated that a novel hypothalamic neuropeptide, neurosecretory protein GL (NPGL), promotes fat accumulation due to the ingestion of sugar by rats. However, differences in lipogenic efficiency of sugar types by NPGL remain unclear. The present study aimed to elucidate the obesogenic effects of NPGL on mice fed different sugars (i.e., sucrose or fructose). We overexpressed the NPGL-precursor gene ( Npgl ) in the hypothalamus of mice fed a medium-fat/medium-sucrose diet (MFSD) or a medium-fat/medium-fructose diet (MFFD). Food intake and body mass were measured for 28 days. Body composition and mRNA expression of lipid metabolic factors were measured at the endpoint. Npgl overexpression potently increased body mass with fat accumulation in the white adipose tissue of mice fed MFFD, although it did not markedly affect food intake. In contrast, we observed profound fat deposition in the livers of mice fed MFFD but not MFSD. In the liver, the mRNA expression of glucose and lipid metabolic factors was affected in mice fed MFFD. Hence, NPGL induced liver steatosis in mice fed a fructose-rich diet.

Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, it is well accepted that the gut plays an important role. To gain more insights into the mechanisms occurring in the different regions of the intestine, adult male mice were fed a high-fat-high sucrose (HFS) diet for 8 days and treated with metformin by gavage (300 mg/day/kg body weight) during the HFS diet. Metformin counteracted HFS diet-induced overexpression of a network of genes involved in the transport of glucose and fatty acids in the different regions of the small intestine. It also induced beneficial modification of secondary bile acid profile in the caecum, with a reduction of deoxycholic acid and lithocholic acid levels and increased abundance of ursodeoxycholic acid and tauroursodeoxycholic acid, potentially leading to FRX inhibition. In parallel, metformin treatment was associated with specific changes of the microbiota composition in the lumen of the different regions of the intestine. Metformin induced a marked increase in the abundance of Akkermansia muciniphila in the lumen all along the gut and counteracted the effects of HFS diet on the abundances of some bacterial groups generally associated with metabolic disturbances (f-Lachnospiraceae, f-Petostreptococcaceae, g-Clostidium). Therefore, the present work clearly emphasises the role of all the regions of the intestinal tract in the beneficial action of the antidiabetic drug metformin in a prediabetic mouse model., (© 2021. The Author(s).)

Fatty acids (FAs) present in the adipose tissue (AT) can be modified by elongases and desaturases. These enzymes are regulated by different factors including nutrients. The aim of the study was to evaluate the impact of high-sucrose diet (HSD; 68% sucrose) on the levels of mRNAs for elongases (Elovl2, Elovl5, Elovl6) and desaturases (Fads1, Fads2, Scd) and on the activity of the corresponding proteins in the rat AT. Male Wistar rats were randomized into two study groups: fed with an HSD and with a standard diet (ST). The mRNA levels were determined by a semi-quantitative reverse transcription-PCR. FA composition was analyzed by gas chromatography, and FA ratios were used to estimate the activity of the enzymes. In the HSD rats, the levels of Elovl5, Elovl6, Fads1, and Scd mRNAs were higher, while the level of Fads2 mRNA was lower than in the ST group. Higher levels of Elovl5 and Elovl6 mRNAs corresponded to higher relative activities of these enzymes, while downregulation of the Fads2 mRNA was associated with the lower activity of this desaturase. In contrast, an increase in the level of Scd mRNA was accompanied by a decrease in the enzyme activity. Less monounsaturated FAs were detected in the AT of HSD rats than in the ST group. The composition of individual FAs differed between the groups. This study supports the notion that the regulation of mRNA levels and activity of both elongases and desaturases play an important role in managing the AT lipid composition in response to changes in the dietary status.

Aims: Liver cirrhosis is the main chronic liver disease and is considered a catabolic disease. Cirrhotic patients have a low energy intake and high energy expenditure at rest, leading to metabolic disorders. Malnutrition is associated with complications of cirrhosis and has been shown that a nutritional intervention with increase of energy intake improves the survival of cirrhotic patients. Therefore, our aim was to evaluate the effect of a high sucrose diet in the liver of animals with cirrhosis induced by thioacetamide and investigate the mechanism involved., Main Methods: Male Wistar rats were divided into three groups: Control; Thioacetamide; and Thioacetamide + high sucrose diet. The thioacetamide was administrated (100 mg kg -1 ) intraperitoneally and the sucrose was offered in drinking water (300 g L -1 )., Key Findings: The administration of thioacetamide was associated with fibrosis and inflammatory infiltrate in the liver and increased levels of transaminases enzymes. The high sucrose diet promoted a reduction of theses parameters in cirrhotic rats. The malnutrition observed in cirrhotic rats was attenuated by the high sucrose diet shown by the improvements in weight loss, subcutaneous fat, and caloric intake. The high sucrose diet also attenuated the oxidative stress present in the liver of animals with thioacetamide-induced cirrhosis., Significance: The high sucrose diet had anti-inflammatory and anti-oxidant effects in the liver of animals with thioacetamide-induced cirrhosis. In addition, the high sucrose diet also improved malnutrition and catabolism present in cirrhosis. Thus, a high sucrose diet may be a therapeutic option for cirrhotic patients in a catabolic state., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Ingesting readily oxidized carbohydrates (CHO) such as sucrose during exercise can improve endurance performance. Whether lactose can be utilized as a fuel source during exercise is unknown. The purpose of this study was to investigate the metabolic response to lactose ingestion during exercise, compared with sucrose or water., Methods: Eleven participants (age, 22 ± 4 yr; V[Combining Dot Above]O2peak, 50.9 ± 4.7 mL·min·kg) cycled at 50% Wmax for 150 min on five occasions. Participants ingested CHO beverages (lactose or sucrose; 48 g·h, 0.8 g·min) or water throughout exercise. Total substrate and exogenous CHO oxidation was estimated using indirect calorimetry and stable isotope techniques (naturally high C-abundance CHO ingestion). Naturally low C-abundance CHO trials were conducted to correct background shifts in breath CO2 production. Venous blood samples were taken to determine plasma glucose, lactate, and nonesterified fatty acid concentrations., Results: Mean exogenous CHO oxidation rates were comparable with lactose (0.56 ± 0.19 g·min) and sucrose (0.61 ± 0.10 g·min; P = 0.49) ingestion. Endogenous CHO oxidation contributed less to energy expenditure in lactose (38% ± 14%) versus water (50% ± 11%, P = 0.01) and sucrose (50% ± 7%, P ≤ 0.05). Fat oxidation was higher in lactose (42% ± 8%) than in sucrose (28% ± 6%; P ≤ 0.01); CHO conditions were lower than water (50% ± 11%; P ≤ 0.05). Plasma glucose was higher in lactose and sucrose than in water (P ≤ 0.01); plasma lactate was higher in sucrose than in water (P ≤ 0.01); plasma nonesterified fatty acids were higher in water than in sucrose (P ≤ 0.01)., Conclusions: Lactose and sucrose exhibited similar exogenous CHO oxidation rates during exercise at moderate ingestion rates. Compared with sucrose ingestion, lactose resulted in higher fat and lower endogenous CHO oxidation.

Knowledge regarding the involvement of sweetness perception on energy intake is scarce. Here, the impact of glucose and sucrose sweetness, beyond their caloric load, on subsequent food intake and biomarkers of satiation was evaluated by co-administration of the sweet taste receptor inhibitor lactisole. A total of 27 healthy, male subjects received solutions of either 10% glucose w / o 60 ppm lactisole or 10% sucrose w / o 60 ppm lactisole. Subsequent food intake from a standardized breakfast was evaluated 2 h after receiving the respective test solution. Changes in postprandial plasma concentrations of cholecystokinin, ghrelin, and serotonin were determined over a period of 120 min, as was the body temperature. Administration of lactisole to the sucrose solution increased the energy intake from the subsequent standardized breakfast by 12.9 ± 5.8% ( p = 0.04), led to a decreased Δ AUC of the body core temperature by 46 ± 20% ( p = 0.01), and time-dependently reduced Δ serotonin plasma concentrations (-16.9 ± 6.06 ng/mL vs. -0.56 ± 3.7 ng/mL after sucrose administration, p = 0.03). The present study shows that lactisole increases energy intake and decreases plasma serotonin concentrations as well as body core temperature induced by sucrose, but not glucose. This finding may be associated with the different binding affinities of sucrose and glucose to the sweet taste receptor.

Continuous feeding of high dietary sugar is strongly associated with type 2 diabetes (T2D) and its secondary complications. Diabetic nephropathy (DN) is a major secondary complication that leads to glomerular and renal tubular dysfunction. The present study is aimed to investigate the effects of chronic exposure of high sugar diet (HSD) on renal tubules. Malpighian tubules (MTs), a renal organ of Drosophila, were used as a model in the study. Feeding of HSD develops T2D condition in Drosophila. The MTs showed structural abnormalities in 20 days of HSD fed flies. Impaired insulin signaling, oxidative stress, enhanced levels of AGE-RAGE and induction of apoptosis were observed in the MTs of these flies. Further, altered expression of transporters, enhanced uric acid level and reduced fluid secretion rate confirmed the impaired function of MTs in these flies. RNA-seq and RT-PCR analyses in the MTs of HSD fed-and control-flies revealed the altered expression of candidate genes that regulate several important pathways including extracellular matrix (ECM), advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), transforming growth factor β (TGF-β), galactose, starch and sucrose metabolism that are well known mediators of renal tubular dysfunction in DN patients. Disruption of insulin signaling in the MTs also causes renal tubular dysfunction similar to HSD fed flies. Overall, the study suggests that phenotypes observed in the MTs of HSD fed flies recapitulate several hallmarks of renal tubular dysfunction in DN patients. Therefore, we conclude that MTs of HSD fed flies may be used for deciphering the underlying mechanisms of T2D mediated renal tubular dysfunction., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Both prenatal and postnatal excessive consumption of dietary sucrose or fructose was shown to be detrimental to health and contributing to pathogenesis of metabolic syndrome. Our knowledge of genetic determinants of individual sensitivity to sucrose-driven metabolic effects is limited. In this study, we have tested the hypothesis that a variation of metabolic syndrome-related gene, Zbtb16 (Zinc Finger and BTB Domain Containing 16 will affect the reaction to high-sucrose diet (HSD) content in "matched" nutritional exposition settings, i.e. maternal HSD with re-exposition to HSD in adulthood vs. standard diet. We compared metabolic profiles of adult males of spontaneously hypertensive rats (SHR) and a single-gene, minimal congenic strain SHR-Zbtb16 fed either standard diet or exposed to HSD prenatally throughout gestation and nursing and again at the age of 6 months for the period of 14 days. HSD exposition led to increased adiposity in both strains and decrease of glucose tolerance and cholesterol (Ch) concentrations in majority of low-density lipoprotein (LDL) particle classes and in very large and large high-density lipoprotein (HDL) in SHR-Zbtb16 male offspring. There was a similar pattern of HSD-induced increase of triacylglycerols in chylomicrons and very low-density lipoprotein (VLDL) of both strains, though the increase of (triacylglycerol) TAG content was clearly more pronounced in SHR. We observed significant STRAIN*DIET interactions for the smallest LDL particles as their TAG content decreased in SHR-Zbtb16 and did not change in SHR in response to HSD. In summary, we provide evidence of nutrigenetic interaction between Zbtb16 and HSD in context of pathogenesis of metabolic syndrome.

Type 2 diabetes mellitus (T2DM) is among the most prevalent diseases in the world, affecting over 420 million people. The disease is marked by a poor metabolic effect of insulin leading to chronic hyperglycaemia, which can result in microvascular complications. It is widely known that postprandial glycaemia is reliant on the total carbohydrate content of a meal. However, the importance of the amount and the source of these carbohydrates remains controversial due to mechanisms other than insulin secretion. Oxidative stress, inflammation, pyruvate production and the quality of the intestinal microbiota, resulting in plasma lipopolysaccharides and short-chain fatty acids production, play an important role in blood sugar control and consequently in type 2 diabetes. Thus, we systematically reviewed the preclinical evidences on the impact of the amount and type of carbohydrate found in different diets and its influence on blood glucose levels in diabetic animals. We used a comprehensive and structured search in biomedical databases Medline (PubMed), Scopus and Web of Science, recovering and analyzing 27 original studies. Results showed that sucrose-rich diets deteriorated diabetic condition in animal models regardless of the total dietary carbohydrate content. On the other hand, fiber, particularly resistant starch, improved blood glucose parameters through direct and indirect mechanisms, such as delayed gastric emptying and improved gut microbiota. All studies used rodents as animal models and male animals were preferred over females. Improvements in T2DM parameters in animal models were more closely related to the type of dietary carbohydrate than to its content on a diet, i. e., resistant starch seems to be the most beneficial source for maintaining normoglycemia. Results show that current literature is at high risk of bias due to neglecting experimental methods., Competing Interests: The authors have declared that no competing interests exist.

Background: Binge eating disorder (BED) is characterized by recurrent binge eating episodes consisting of rapid consumption of excessive amounts of highly palatable, energy-dense food within discrete periods of time. The aim of this study was to test the consummatory, food microstructural, and metabolic effects of a one hour limited access to either a high-sucrose diet (HSD) or a high-fat diet (HFD) in an operant rat model of binge-like eating., Methods: Female rats were subject to a binge-like eating procedure in which a HSD, a HFD, or a standard chow diet were provided in a fixed ratio 1 (FR1) operant schedule of reinforcement., Results: Limiting access to either a HSD or a HFD promoted binge-like eating as compared to the control chow diet. However, binge-like eating of HSD, but not HFD, was based on a true increase in the amount of food consumed, an increased eating rate, and a decrease in the intake of the home-cage standard chow, altogether suggesting an increase in palatability. Moreover, while HSD rats consumed overall less energy than HFD rats, the former were more energy efficient and gained more body weight than the latter., Conclusions: These results provide information on how the quality of food can deeply influence the behavioral and metabolic outcomes of binge-like eating.

Early life exposure to certain environmental stimuli is related to the development of alternative phenotypes in mammals. A number of these phenotypes are related to an increased risk of disease later in life, creating a massive healthcare burden. With recent focus on the determination of underlying causes of common metabolic disorders, parental nutrition is of great interest, mainly due to a global shift towards a Western-type diet. Recent studies focusing on the increase of food or macronutrient intake don't always consider the source of these nutrients as an important factor. In our study, we concentrate on the effects of high-sucrose diet, which provides carbohydrates in form of sucrose as opposed to starch in standard diet, fed in pregnancy and lactation in two subsequent generations of spontaneously hypertensive rats (SHR) and congenic SHR-Zbtb16 rats. Maternal sucrose intake increased fasting glycaemia in SHR female offspring in adulthood and increased their chow consumption in gravidity. High-sucrose diet fed to the maternal grandmother increased brown fat weight and HDL cholesterol levels in adult male offspring of both strains, i.e., the grandsons. Fasting glycaemia was however decreased only in SHR offspring. In conclusion, we show the second-generation effects of maternal exposition to a high-sucrose diet, some modulated to a certain extent by variation in the Zbtb16 gene.

Background: Sugar-sweetened drinks (SSDs) are known to be cariogenic, but this association has not been well investigated in population-based repeated cross-sectional studies in recent years. Therefore, this study examined whether SSD intake is associated with higher caries experience in 10- and 15-year-olds., Methods: The study sample included participants from the Munich study centre of two birth cohorts with data on non-cavitated caries lesions (NCCL/S), caries experience (DMF/S index), overall caries burden (DMF + NCCL/S) and SSD intake. In total, 915 and 996 children were included from the 10- and 15-year follow-ups, respectively. Intake (g/day) of SSDs, comprising cola, lemonade, ice-tea, sport/energy drinks, fruit squashes and nectars, was calculated from food frequency questionnaires. For analyses, the SSD intake was converted into portions (250 ml/day). Multiple logistic regression and prospective analysis models were performed to test associations between SSD intake and various definitions of caries, adjusting for sex, parental education, body mass index (BMI) categories, study cohort, plaque-affected sextants, mode of SSD consumption, energy content of SSDs, and total energy intake., Results: The mean overall caries burden at 10 and 15 years of age was 1.81 (SD: 2.71) and 6.04 (SD: 8.13), respectively. The average consumption of SSDs at the 10- and 15-year follow-ups was 0.48 (SD: 0.85) and 0.83 (SD 1.40) portions/day, respectively. After adjusting for confounders, in 10-year-olds, SSD intake was significantly associated with higher caries experience based on the indices DMF/S (adjusted odds ratio: 1.29; 95% CI: 1.06-1.57), NCCL/S (1.24; 1.03-1.49) and DMF + NCCL/S (1.27; 1.05-1.55). At the 15-year follow-up, SSD consumption was significantly associated with increased DMF/S index (1.12; 1.01-1.25) only. Prospective model associating 10-year SSD intake with 15-year caries experience was not significant., Conclusions: SSD intake significantly increases the caries burden in 10-year-olds, with attenuated effects in 15-year-olds. To prevent caries, SSD consumption should be reduced, especially in children and adolescents.

The dietary nutrient composition can affect insects' phenotypes by modulating their physiology. Furthermore, diet can affect gut microbiota composition and abundance, with indirect consequences for the host. In this study, we reared Drosophila melanogaster on five different diets; three with balanced sugar:yeast ratio, but with increasing caloric content (2:2, 8:8, 16:16, in weight %), and two with imbalanced sugar:yeast ratio, either with low sugar and high yeast content (2:16) or vice-versa (16:2). In each of these diets, we compared flies with conventional vs. artificially altered gut microbiota with antibiotics that reduced the bacterial load. The antibiotic treatment also had the surprising effect of increasing the amount of live yeast associated with the flies. We characterized flies from these ten treatments (5 diets × 2 microbiota) in terms of development, body mass, food preference, body reserves, metabolic rate and a range of stress tolerance traits (heat, cold, starvation and desiccation tolerance). Diets, and to a lesser extent antibiotic treatment, affected development rate, weight, and cold tolerance of adult flies. Other traits such as energy reserves, metabolic rate, food preference, or starvation tolerance were affected by diet alone. When detected, the effect of antibiotic treatment was stronger in yeast-poor diets, suggesting that gut bacterial community might help to counterbalance nutritional deficiencies. These results show that changes in dietary factors lead to a global re-organization of fly's physiology and development while the manipulation of gut microorganisms had minor effects that were mainly seen in case of protein restriction., Competing Interests: Declaration of Competing Interest Authors have no conflict of interest to declare., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Metabolic syndrome has become a global health challenge and was recently reported to be positively correlated with increased sucrose consumption. Mechanistic analyses of excess sucrose-induced progression of metabolic syndrome have been focused mainly on abnormal hepatic lipogenesis, and the exact contribution of excess sucrose to metabolic disorders remains controversial. Considering that carbohydrate and lipid metabolisms exhibit clear circadian rhythms, here we investigated the possible contribution of diurnal oscillations to responses of hepatic lipid metabolism to excess sucrose. We found that excess sucrose dose-dependently promotes fatty liver and hyperlipidemia in in rats fed a high-sucrose diet (HSD). We observed that excess sucrose enhances the oscillation amplitudes of the expression of clock genes along with the levels of hepatic lipid and carbohydrate metabolism-related mRNAs that increase lipogenesis. We did not observe similar changes in the levels of the transcription factors regulating the expression of these genes. This suggested that the excess sucrose-induced, circadian rhythm-dependent amplification of lipogenesis is post-transcriptionally regulated via the stability of metabolic gene transcripts. Of note, our findings also provide evidence that fructose causes some of the HSD-induced, circadian rhythm-dependent alterations in lipogenic gene expression. Our discovery of HSD-induced circadian rhythm-dependent alterations in lipogenesis at the post-transcriptional level may inform future studies investigating the complex relationships among sucrose uptake, circadian rhythm, and metabolic enzyme expression. Our findings could contribute to the design of chrono-nutritional interventions to prevent or manage the development of fatty liver and hyperlipidemia in sucrose-induced metabolic syndrome., (© 2019 Sun et al.)

Objective: Although it is widely accepted that obesity results from an imbalance of energy intake and expenditure, the mechanisms underlying this process and effective strategies for prevention and treatment are unclear. Growing evidence suggests excess consumption of sugar may play an important role, yet we showed previously in mice that consuming up to 30% of calories as sucrose in the diet had no impact on weight regulation. Since in humans consumption of sugar-sweetened beverages has been widely implicated, we investigated whether the mode of ingestion (solid or liquid) had different impacts on body weight regulation and glucose homeostasis., Methods: Dietary sucrose was delivered in solid (as part of a standard pelleted rodent chow) and liquid (in drinking water) to C57BL/6 mice for 8 weeks. Body weight, body composition, energy intake and expenditure were monitored, as well as glucose and insulin tolerance tests. Expression of sweet taste receptors on the tongue, and glycogen and fat contents of the liver were also measured., Results: Consumption of sucrose-sweetened water, but not equivalent levels of solid sucrose, led to body fat gain in C57BL/6 mice. Glucose intolerance was positively correlated to body fatness, rather than sucrose intake., Conclusions: Our data support the suggestion that consumption of liquid sucrose may be an important contributor to dysregulation of body weight and related metabolic syndromes., (Copyright © 2019. Published by Elsevier GmbH.)

Consumption of dietary bioactives is an avenue to enhancing the effective healthiness of diets by attenuating the glycaemic response. The intestinal brush border enzyme sucrase-isomaltase (SI) is the sole enzyme hydrolysing consumed sucrose, and we previously showed the acute effects of olive leaf extract (OLE) on sucrase activity when given together with sugars both in vitro and in vivo. Here we tested whether OLE could affect sucrase expression when pre-incubated chronically, a "priming" effect not dependent on competitive interaction with SI, in both a cell model and a human intervention. Using differentiated Caco-2/TC7 cells, long-term pre-treatment with oleuropein-rich olive leaf extract (OLE) lowered SI mRNA, surface protein and activity, and attenuated subsequent sucrose hydrolysis. Based on these results, a randomised, double-blinded, placebo-controlled, crossover pilot study was conducted. OLE (50 mg oleuropein) was consumed in capsule form 3 times a day for 1 week by 11 healthy young women followed by an oral sucrose tolerance test in the absence of OLE. However this treatment, compared to placebo, did not induce a change in post-prandial blood glucose maximum concentration (Glc max ), time to reach Glc max and incremental area under the curve. These results indicate that changes in SI mRNA, protein and activity in an intestinal cell model by OLE are not sufficient under these conditions to induce a functional effect in vivo in healthy volunteers.

Excessive sucrose intake, known as fructose toxicity, leads to fatty liver, hyperlipidemia, and metabolic syndrome. Circadian disorders also contribute to metabolic syndrome. Here, we investigated the effect of excessive sucrose intake on circadian rhythms of the small intestine, the main location of sucrose absorption, to elucidate a mechanism of sucrose-induced abnormal lipid metabolism. Male Wistar rats were fed control starch or high-sucrose diets for 4 weeks. High-sucrose diet-induced fatty liver and hypertriglyceridemia in rats. Amplitudes of PER1/2 expression oscillations in the small intestine were reduced by excessive sucrose, while gene expression of GLUT5 and gluconeogenic enzymes was enhanced. These changes would contribute to interfering in lipid homeostasis as well as adaptive responses to control fructose toxicity in rats.

Objectives: Glucagon-like peptide-1 (GLP-1) is secreted by enteroendocrine L-cells in response to nutrient ingestion. To date, GLP-1 secretion in diet-induced obesity is not well characterized. We aimed to examine GLP-1 secretion in response to meal ingestion during the progression of diet-induced obesity and determinewhether a combined high-fat and high-sucrose (HFS) diet, an individual high-fat (HiFat), or a high-sucrose (HiSuc) diet affect adaptive changes in the postprandial GLP-1 response., Methods: Rats were fed a control, HiFat diet (30% weight), HiSuc diet (40% weight), or HFS (30% fat and 40% sucrose) diet for 5 wk. Meal tolerance tests were conducted to determine postprandial glucose, insulin, and GLP-1 responses to standard (control) diet ingestion every 2 wk., Results: After 5 wk, body weight gain of the HiFat (232.3 ± 7.8 g; P = 0.021) and HFS groups (228.0 ± 7.8; P = 0.039), but not the HiSuc group (220.3 ± 7.9; P = 0.244), were significantly higher than that of the control group (200.7 ± 5.4 g). In meal tolerance tests after 2 wk, GLP-1 concentration was significantly elevated in the HFS group only (17.2 ± 2.6 pM; P < 0.001) in response to meal ingestions, but the HiFat group (16.6 ± 3.7 pM; P = 0.156) had a similar response as the HFS group. After 4 wk, GLP-1 concentrations were similarly elevated at 15min in the HFS (14.1 ± 4.4; P = 0.010), HiFat (13.2 ± 2.0; P < 0.001), and HiSuc (13.0 ± 3.3; P = 0.016) groups, but the HFS (9.8 ± 1.0; P = 0.019) and HiFat (8.3 ± 1.5; P = 0.010) groups also had significant elevation at 30min., Conclusions: These results demonstrate that the continuous ingestion of excessive fat and sucrose rapidly enhances the GLP-1 secretory response to luminal nutrients, and the HiFat diet may have a potent effect compared with the HiSuc diet on GLP-1 secretory responses. The increment of postprandial GLP-1 and insulinsecretion may have a role in normalizing postprandial glycaemia and slowing the establishment of glucose intolerance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The main objective of these studies was to characterize metabolic, body composition, and cardiovascular responses to a free-choice high-fat, high-sucrose diet in female cycling and pregnant rats. In the nonpregnant state, female Sprague-Dawley rats offered a 3-wk free-choice high-fat, high-sucrose diet had greater energy intake, adiposity, serum leptin, and triglyceride concentrations compared with rats fed with standard chow and developed glucose intolerance. In addition, choice-diet-fed rats had larger cardiac ventricular weights, smaller kidney and pancreas weights, and higher blood pressure than chow-fed rats, but they did not exhibit resistance artery endothelial dysfunction. When the free-choice diet continued throughout pregnancy, rats remained hyperphagic, hyperleptinemic, and obese. Choice pregnant rats exhibited uterine artery endothelial dysfunction and had smaller fetuses compared with chow pregnant rats. Pregnancy normalized mean arterial blood pressure and pancreas weights in choice rats. These studies are the first to provide a comprehensive evaluation of free-choice high-fat, high-sucrose diet on metabolic and cardiovascular functions in female rats, extending the previous studies in males to female cycling and pregnant rodents. Free-choice diet may provide a new model of preconceptual maternal obesity to study the role of increased energy intake, individual food components, and preexisting maternal obesity on maternal and offspring physiological responses during pregnancy and after birth.

Purpose: The positional analysis of hepatic glycogen enrichment from deuterated water ( 2 H 2 O) by 2 H NMR has been applied previously to resolve the contributions of glucose and fructose to glycogen synthesis in rodents fed a high sucrose diet. To further validate this method, this analysis was applied to mice fed with synthetic diets whose carbohydrate components consisted solely of either glucose or fructose., Methods: Eight glucose-fed and 12 fructose-fed mice were given 2 H 2 O followed by ad libitum feeding overnight. Mice were then euthanized, hepatic glycogen was isolated and derivatized to monoacetone glucose, and 2 H-enrichment of positions 2, 5, and 6 S were measured by 2 H NMR. From these data, the fraction of overnight glycogen appearance from the direct pathway and/or glycogen cycling and indirect pathway were estimated. Indirect pathway fractions were resolved into Krebs cycle and triose-phosphate sources-the latter including contributions from fructose metabolism., Results: After overnight feeding, the fraction of overnight glycogen appearance derived from direct pathway and/or glycogen cycling in glucose-fed-mice was 63 ± 1%. For the indirect pathway, Krebs cycle and triose-phosphate sources contributed 22 ± 1% and 15 ± 1%, respectively. For fructose-fed-mice, glycogen appearance was dominated by triose-phosphate sources (60 ± 2%) with lesser contributions from Krebs cycle (14 ± 1%) and direct and/or glycogen cycling (26 ± 2%)., Conclusions: 2 H NMR analysis of hepatic glycogen 2 H enrichment from 2 H 2 O provides realistic profiles of dietary glucose and fructose contributions to hepatic glycogen synthesis in mice fed with diets containing 1 or the other sugar as the sole carbohydrate source., (© 2018 International Society for Magnetic Resonance in Medicine.)

Background: The presence of the neonicotinoid imidacloprid in nectar, honey, pollen, beebread and beeswax has been implicated in declines worldwide in the health of the western honey bee Apis mellifera. Certain phytochemicals, including quercetin and p-coumaric acid, are ubiquitous in the honey bee diet and are known to upregulate cytochrome P450 genes encoding enzymes that detoxify insecticides. Thus, the possibility exists that these dietary phytochemicals interact with ingested imidacloprid to ameliorate toxicity by enhancing its detoxification., Approach: Quercetin and p-coumaric acid were incorporated in a phytochemical-free artificial diet individually and together along with imidacloprid at a range of field-realistic concentrations. In acute toxicity bioassays, honey bee 24- and 48- hour imidacloprid LC50 values were determined in the presence of the phytochemicals. Additionally, chronic toxicity bioassays were conducted using varying concentrations of imidacloprid in diets with the phytochemicals to test impacts of phytochemicals on longevity., Results: In acute toxicity bioassays, the phytochemicals had no effect on imidacloprid LC50 values. In chronic toxicity longevity bioassays, phytochemicals enhanced honey bee survival at low imidacloprid concentrations (15 and 45 ppb) but had a negative effect at higher concentrations (105 ppb and 135 ppb). p-Coumaric acid alone increased honey bee longevity at concentrations of 15 and 45 ppb imidacloprid (hazard ratio (HR): 0.83 and 0.70, respectively). Quercetin alone and in combination with p-coumaric acid similarly enhanced longevity at 45 ppb imidacloprid (HR:0.81 and HR:0.77, respectively). However, p-coumaric acid in combination with 105 ppb imidacloprid and quercetin in combination with 135 ppb imidacloprid increased honey bee HR by approximately 30% (HR:1.33 and HR:1.30, respectively)., Conclusions: The biphasic concentration-dependent response of honey bees to imidacloprid in the presence of two ubiquitous dietary phytochemicals indicates that there are limits to the protective effects of the natural diet of honey bees against neonicotinoids based on their own inherent toxicity., Competing Interests: The authors have declared that no competing interests exist.

The effect that blood glucose concentration has on feelings of satiety is unclear. Our aims were to assess satiety and subsequent energy intake following the ingestion of trifle sweetened with sucrose or isomaltulose whilst measuring plasma glucose concentration to confirm glycemic differences between trifles. Seventy-seven healthy adults participated in a double-blind crossover trial where trifle sweetened with sucrose or isomaltulose was consumed on separate days with a two-week washout. Blood was sampled at the baseline, 1 and 2 h postprandially, and satiety assessed using visual analogue scales (VAS). Weighed diet records were taken on test days. A statistically significant difference in blood glucose concentration between trifles was found at 60 min following consumption, with the isomaltulose trifle having a 0.69 mmol/L (95% confidence interval: -1.07, -0.31) lower concentration when compared with the sucrose trifle. Mean satiety response by area-under-the-curve (AUC) was not significantly different between trifles. Mean (SD) appetite scores for the sucrose and isomaltulose trifles were 4493 (2393) and 4527 (2590) mm·min, respectively, with a between trifle difference of -9 (95% CI: -589, 572) mm·min. Mean (SD) energy intake for the remainder of the day following trifle consumption was 3894 kJ (1950 kJ) and 3530 kJ (1926 kJ) after the sucrose and isomaltulose trifles, respectively, and was not significantly different ( p = 0.133). The differing glycemic response to trifle was not related to satiety or to subsequent energy intake.

Hypertensive subjects often exhibit exaggerated cardiovascular reactivity. An overactive orexin system underlies the pathophysiology of hypertension. We examined orexin's roles in eating-associated cardiovascular reactivity in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Results showed eating regular chow or palatable food (sucrose agar) was accompanied by elevated arterial pressure and heart rate. In both SHRs and WKY rats, the cardiovascular responses associated with sucrose-agar consumption were greater than that with regular-chow consumption. Additionally, SHRs exhibited greater cardiovascular responses than WKY rats did to regular-chow and palatable food consumption. Central orexin 2 receptor (OX2R) blockade attenuated sucrose-agar consumption-associated cardiovascular response only in SHRs. In both SHRs and WKY rats, OX2R blockade did not affect regular-chow consumption-associated cardiovascular responses. Greater numbers of c-Fos-positive cells in the rostral ventrolateral medulla (RVLM) and of c-Fos-positive orexin neurons in the dorsomedial hypothalamus (DMH) were detected in sucrose agar-treated SHRs, compared to regular chow-treated SHRs and to sucrose agar-treated WKY rats. Central OX2R blockade reduced the number of c-Fos-positive cells in the RVLM only in sucrose agar-treated SHRs. We concluded that in SHRs, orexin neurons in the DMH might be overactive during eating palatable food and may further elicit exaggerated cardiovascular responses via an OX2R-RVLM pathway.

In endothermic wasps, foraging is an expensive activity. To maximise the benefit for the colony, wasps can optimise either the intake rate or energetic efficiency of a foraging trip. We investigated the foraging behaviour of vespine wasps under variable environmental and reward conditions. We trained them to forage for 0.5 mol l -1 sucrose solution from an artificial flower in a flow-through respiratory measurement chamber, and simultaneously measured their body temperature using infrared thermography to investigate interactions between thermoregulation and energetics. Measurement of carbon dioxide release (for energetic calculations) and load mass enabled the direct determination of foraging efficiency. An unlimited reward increased the wasps' energetic effort to increase the suction speed through high body temperatures. With reduced reward (limited flow), when an increased body temperature could not increase suction speed, the wasps decreased their body temperature to reduce the metabolic effort. Solar heat gain was used differently, either to increase body temperature without additional metabolic effort or to save energy. The foraging efficiency was mainly determined by the flow rate, ambient temperature and solar heat gain. In shade, an unlimited sucrose flow and a high ambient temperature yielded the highest energetic benefit. A limited flow reduced foraging efficiency in the shade, but only partly in sunshine. Solar radiation boosted the efficiency at all reward rates. Wasps responded flexibly to varying reward conditions by maximising intake rate at unlimited flow and switching to the optimisation of foraging efficiency when the intake rate could not be enhanced due to a limited flow rate., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

The glycaemic index (GI) is a useful tool to compare the glycaemic responses of foods. Numerous studies report the favorable effects of low GI diets on long term metabolic health compared with high GI diets. However, it has not been possible to link these effects to the GI itself because of other components such as macronutrients and dietary fibre, which are known to affect GI. This study aimed to create and evaluate isocaloric diets differing in GI independent of macronutrient and fibre content. The GIs of eight diets differing in carbohydrate source were evaluated in mice; cooked cornstarch (CC), raw cornstarch (RC), chow, maltodextrin, glucose, sucrose, isomaltulose, and fructose. A glucose control was also tested. The GIs of all eight diets were different from the GI of the glucose control (GI: 100; p < 0.0001). The GIs of the glucose (mean ± SEM: 52 ± 3), maltodextrin (52 ± 6), CC (50 ± 4), RC (50 ± 6), and chow (44 ± 4) diets were similar, while the GIs of the sucrose (31 ± 4), isomaltulose (24 ± 5), and fructose (18 ± 2) diets were lower than all other diets ( p < 0.05). This is the first trial to report GI testing in vivo in mice, resulting in three main findings: chow is relatively high GI, the glucose availability of raw and cooked cornstarch is similar, and the GI of different sugar diets occur in the same rank order as in humans.

Background: This population-based study was designed to investigate whether consumption of sugar-sweetened beverages (SSB) is associated with lower serum total testosterone concentration in men 20-39 years old., Methods: All data for this study were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. The primary outcome was serum testosterone concentration, and main independent variable was SSB intake. Other variables included age, race/ethnicity, poverty/income ratio, body mass index (BMI), serum cotinine, heavy drinking, and physical activity., Results: Among all subjects (N = 545), 486 (90.4%) had normal testosterone levels (defined as ≥231 ng/dL) and 59 (9.6%) had low testosterone levels (defined as < 231 ng/dL). Multivariate logistic regression revealed the odds of low testosterone was significantly greater with increasing SSB consumption (Q4 [≥442 kcal/day] vs. Q1 [≤137 kcal/day]), adjusted odds ratio [aOR] = 2.29, p = 0.041]. After adjusting for possible confounding variables, BMI was an independent risk factor for low testosterone level; subjects with BMI ≥ 25 kg/m 2 had a higher risk of having a low testosterone level than those with BMI < 25 kg/m 2 (aOR = 3.68, p = 0.044)., Conclusion: SSB consumption is significantly associated with low serum testosterone in men 20-39 years old in the United States.

Little is still known about brain protein synthesis. In order to increase our knowledge of it, we aimed to modulate brain protein synthesis rates through aging, variations in nutritional state (fed state vs. fasted state), high sucrose diet and micronutrient supplementation. Four groups of 16 month-old male rats were fed for five months with a diet containing either 13% or 62% sucrose (wheat starch was replaced with sucrose), supplemented or not with rutin (5 g kg-1 diet), vitamin E (4×), A (2×), D (5×), selenium (10×) and zinc (+44%) and compared with an adult control group. We measured cerebellum protein synthesis and hippocampus gene expression of antioxidant enzymes, inflammatory cytokines and transcription factors. We showed that cerebellum protein synthesis was unchanged by the nutritional state, decreased during aging (-8%), and restored to the adult level by micronutrient supplementation. Sucrose diet did not change protein synthesis but reduced the protein content. Micronutrient supplementation had no effect in sucrose fed rats. Hippocampus gene expressions were affected by age (an increase of TNF-α), sucrose treatment (an increase of IL-1β and IL-6), and micronutrient supplementation (a decrease of heme oxygenase, catalase, glutathione peroxidase, TNF-α, and Nrf2). We noted that cerebellum protein synthesis and hippocampus TNF-α gene expression were modulated by the same factors: they were affected by aging and micronutrient supplementation and unchanged by feeding and by high sucrose diet.

This work aims to assess the possible beneficial effects of dietary fish oil (FO) on the pre-existing adipose tissue dysfunction through the improvement or reversion of the mechanisms underlying oxidative stress and pro-inflammatory cytokines in dyslipemic insulin-resistant rats. Wistar rats were fed a sucrose rich diet (SRD) for 6 months. After that half of the animals continued with the SRD until month 8 while in the other half corn oil was replaced by FO for 2 months (SRD + FO). A reference group consumed a control diet all the time. In an epididymal fat pad, we analyzed antioxidant and oxidant enzyme activities, ROS content, glutathione redox state, the protein level of peroxisome proliferator-activated receptor gamma (PPARγ) and the expression and protein levels of uncoupling protein 2 (UCP2) as well as oxidative stress biomarkers and TNF-α and IL-6 plasma levels. Besides these, insulin sensitivity and the composition of fatty acid phospholipids of adipose tissue were measured. Compared with the SRD the SRD + FO fed group showed a decrease of fat pad weight and the antioxidant and oxidant enzyme activities and ROS content returned to control values along with normal plasma TNF-α and IL-6 levels. FO normalized both the decrease of PPARγ protein and the increase of protein and expression of UCP2. Furthermore, FO increased the n-3/n-6 fatty acid ratio in the adipose tissue phospholipids and normalized dyslipidemia and insulin resistance. Finally, these findings reinforce the view that dietary FO may exert a beneficial effect in ameliorating the dyslipidemia and insulin resistance in this animal model.

We have reported that motivation for sucrose is increased in rats fed a moderate (31%) mixed-fat diet for 4-6 wk. In this study, rats were fed diets containing 32% stearic (STEAR) or palmitic (PALM) acid, and behavior, metabolic profile, and cell signals were compared with those of rats fed a matched low-fat diet (LF; 11% fat) diet. Rats fed STEAR or PALM increased sucrose motivation relative to LF rats (one-way ANOVA for lever presses; P = 0.03). Diet did not change fasting glucose, insulin, total cholesterol, triglycerides, intravenous glucose tolerance test glucose profile, percent body fat, or total kilocalories, although kilocalories as fat were increased (ANOVA, P < 0.05). Cell signals were assessed in rats ranked from high to low sucrose motivation. Diet did not alter Thr and Ser phosphorylation of Akt in the medial hypothalamus (HYP) and striatum (STR). However, Ser phosphorylation of GSK3Β was decreased in HYP and STR from both high- and low-performer tertiles of STEAR and PALM rats (ANOVA within each brain region, P < 0.05). Two histone 3 (H3) modifications were also assessed. Although there was no effect of diet on the transcription-repressive H3 modification, H3K27me3, the transcription-permissive H3 modification, H3K4me3, was significantly decreased in the HYP of high performers fed PALM or STEAR (ANOVA, P = 0.013). There was no effect of diet on H3K4me3 levels in HYP of low performers, or in STR. Our findings suggest signal-specific and brain region-specific effects of PALM or STEAR diets and may link downstream signaling effects of GSK3Β activity and H3 modifications with enhanced motivational behavior.

During preclinical development of canagliflozin, an SGLT2 inhibitor, treatment-related pheochromocytomas, renal tubular tumors (RTT), and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. In a previous 6-month rat mechanistic study, feeding a glucose free diet prevented canagliflozin effects on carbohydrate malabsorption as well as the increase in cell proliferation in adrenal medulla and kidneys, implicating carbohydrate malabsorption as the mechanism for tumor formation. In this chronic study male Sprague-Dawley rats were dosed orally with canagliflozin at high dose-levels (65 or 100 mg/kg/day) for 15 months and received either a standard diet or a glucose-free diet. Canagliflozin-dosed rats on standard diet showed presence of basophilic renal tubular tumors (6/90) and an increased incidence of adrenal medullary hyperplasia (35/90), which was fully prevented by feeding a glucose-free diet (no RTT's; adrenal medullary hyperplasia in ≤5/90). These data further confirm that kidney and adrenal medullary tumors in the 2-year rat study were secondary to carbohydrate (glucose) malabsorption and were not due to a direct effect of canagliflozin on these target tissues., (Copyright © 2017 Elsevier B.V. All rights reserved.)

High sugar consumption elicits numerous deleterious effects on health by inducing insulin resistance, which is closely associated with the development of metabolic disorders such as obesity or type-2 diabetes. Furthermore, there is also growing evidence that caffeine may play an important role in the regulation of insulin release and the appearance of related metabolic impairments. Thus, the aim of this work was to investigate the impact of acute sugar and caffeine intake on the metabolic health status by using a metabolomic multi-platform based on the combination of flow injection mass spectrometry and ultra-high performance liquid chromatography mass spectrometry. To this end, we performed a randomized, crossover and double-blind intervention study with different soft drinks from the same brand. Numerous metabolomic changes were detected in serum samples over time after the intake of sugar-sweetened beverages, including energy-related metabolites, amino acids and lipids, thus demonstrating the intense effects provoked by acute sugar consumption on the organism during 3 h of follow-up. However, the most significant findings were observed after the co-ingestion of caffeine, which could be indicative of a synergic effect of this psychostimulant on insulin-mediated perturbations., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dietary polyphenols have been shown to inhibit α-glucosidase, an enzyme target of some antidiabetic drugs. Resveratrol, a polyphenol found in grapes and wine, has been reported to inhibit the activity of yeast α-glucosidase. This triggered our interest to synthesize analogs and determine their effect on mammalian α-glucosidase activity. Using either sucrose or maltose as substrate resveratrol, piceatannol and 3'-hydroxypterostilbene showed strong inhibition of mammalian α-glucosidase activity; pinostilbene, cis-desoxyrhapontigenin and trans-desoxyrhapontigenin had moderate inhibition. Compared to acarbose (IC 50 3-13 μg/ml), piceatannol and resveratrol inhibited mammalian α-glucosidase to a lesser extent (IC 50 14-84 and 111-120 μg/ml, respectively). 3'-Hydroxypterostilbene (IC 50 105-302 μg/ml) was 23-35-fold less potent than acarbose. We investigated the effect of piceatannol and resveratrol on postprandial blood glucose response in high-fat-fed C57Bl/6 mice. Animals administered resveratrol (30 mg/kg body weight [BW]) or piceatannol (14 mg/kg BW) 60 min prior to sucrose or starch loading had a delayed absorption of carbohydrates, resulting in significant lowering of postprandial blood glucose concentrations, similar to the antidiabetic drug acarbose, while no significant effect was observed with the glucose-loaded animals. Our studies demonstrate that the dietary polyphenols resveratrol and piceatannol lower postprandial hyperglycemia and indicate that inhibition of intestinal α-glucosidase activity may be a potential mechanism contributing to their antidiabetic property., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The peripheral sensitivity and palatability of different carbohydrates was evaluated and their nutritional value assessed in adult females of D. suzukii by means of an electrophysiological, behavioural and metabolic approach. The electrophysiological responses were recorded from the labellar "l" type sensilla stimulated with metabolizable mono- and disaccharides (glucose and maltose) and a non-metabolizable sugar (sucralose); the response rating and the palatability to the same sugars, evaluated by recording the proboscis extension reflex (PER), was maltose>glucose>sucralose. The nutritional value of carbohydrates was assessed by means of survival trials and fatty acids profile. Flies fed on a diet containing maltose had a longer lifespan than flies on monosaccharides, while flies fed on a diet containing sucralose had a shorter one. In addition, the ability to store fat seems to be influenced by the different sugars in the diet and is in relationship with their palatability. In fact, data showed a higher synthesis of palmitic and palmitoleic acids, most likely derived from de-novo lipogenesis with glucose as precursor, in flies fed with maltose and glucose than with non-metabolizable sucralose. In conclusion, these results suggest that the ability to select different sugars on the basis of their palatability may favour the storage of energy reserves such as fat by de-novo lipogenesis, determining a longer survival capability during prolonged periods of fasting.

The taste reactivity test is considered as an objective measure to assess the hedonic impact of tastes. Both the appetitive and aversive pattern of responses are plastic and can change based on previous experience. The present study assessed the repertoire of taste responses elicited by sucrose and quinine in preweanling rats, and described changes in these taste reactivity patterns after exposure to the other tastant. We exposed infant rats (17 days old at the start of training) to sweet (2% sucrose) or bitter (0.01% quinine) tastants during 4, 10-min trials in two different random sequences. The subjects were weighed before and after each trial to provide a measure of percent body weight gained. The following taste reactivity responses were registered: duration of mouthing and paw lick, frequency of chin rub, head shake and flailing of the forelimbs, frequency and duration of face washing, wall climbing and paw tread. The consummatory and affective taste responses changed depending on the order in which the solutions were administered. The order of exposure to the tastants did not affect the levels of sucrose intake. Conversely, rat pups showed more ingestive, and fewer aversive, responses to the sweet tastant when access to the solution followed the intraoral infusion of quinine. Likewise, intraoral delivery of quinine elicited a more aversive taste reactivity pattern when delivered after the access to sucrose than when presented to sucrose-naïve pups. This research contributes to the analysis of taste reactivity responses during the early ontogeny of the rat and highlights the importance of previous experiences on the subsequent assessment of rewards., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Food flavour is important in appetite control. The effects of aroma and taste, independently or in combination, on appetite sensation and subsequent food intake, were studied. Twenty-six females (24 ± 4 years, 20.9 ± 1.9 kg⋅m -2 ) consumed, over 15 min period, one of four sample drinks as a preload, followed by an ad libitum consumption of a pasta meal (after 65 min). Sample drinks were: water (S1, 0 kcal), water with strawberry aroma (S2, 0 kcal), water with sucrose and citric acid (S3, 48 kcal) and water with strawberry aroma, sucrose and citric acid (S4, 48 kcal). Appetite sensation did not differ between the S1 (water), S2 (aroma) and S3 (taste) conditions. Compared with S1 (water), S2 (aroma) and S3 (taste), S4 (aroma + taste) suppressed hunger sensation over the 15 min sample drink consumption period (satiation) (p < 0.05). S4 (aroma + taste) further reduced hunger sensation (satiety) more than S1 at 5, 20 and 30 min after the drink was consumed (p < 0.05), more than S2 (aroma) at 5 and 20 min after the drink was consumed (p < 0.05), and more than S3 (taste) at 5 min after the drink was consumed (p < 0.05). Subsequent pasta energy intake did not vary between the sample drink conditions. S4 (aroma + taste) had the strongest perceived flavour. This study suggests that the combination of aroma and taste induced greater satiation and short-term satiety than the independent aroma or taste and water, potentially via increasing the perceived flavour intensity or by enhancing the perceived flavour quality and complexity as a result of aroma-taste cross-modal perception., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Extreme diets consisting of either high fat (HF) or high sucrose (HS) may lead to insulin resistance in skeletal muscle, often associated with mitochondrial dysfunction. However, it is not known if these diets alter normal interactions of pyruvate and fatty acid oxidation at the level of the mitochondria. Here, we report that rat muscle mitochondria does show the normal Randle-type fat-carbohydrate interaction seen in vivo. The mechanism behind this metabolic flexibility at the level of the isolated mitochondria is a regulation of the flux-ratio: pyruvate dehydrogenase (PDH)/ β -oxidation to suit the actual substrate availability, with the PDH flux as the major point of regulation. We further report that this regulatory mechanism of carbohydrate-fat metabolic interaction surprisingly is lost in mitochondria obtained from animals exposed for 12 weeks to a HF- or a HS diet as compared to rats given a normal chow diet. The mechanism seems to be a loss of the PDH flux decrease seen in controls, when fatty acid is supplied as substrate in addition to pyruvate, and vice versa for the supply of pyruvate as substrate to mitochondria oxidizing fatty acid. Finally, we report that the calculated TCA flux in the isolated mitochondria under these circumstances shows a significant reduction (~50%) after the HF diet and an even larger reduction (~75%) after the HS diet, compared with the chow group. Thus, it appears that obesogenic diets as those applied here have major influence on key metabolic performance of skeletal muscle mitochondria., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Nectar-feeding animals have among the highest recorded metabolic rates. High aerobic performance is linked to oxidative damage in muscles. Antioxidants in nectar are scarce to nonexistent. We propose that nectarivores use nectar sugar to mitigate the oxidative damage caused by the muscular demands of flight. We found that sugar-fed moths had lower oxidative damage to their flight muscle membranes than unfed moths. Using respirometry coupled with δ 13 C analyses, we showed that moths generate antioxidant potential by shunting nectar glucose to the pentose phosphate pathway (PPP), resulting in a reduction in oxidative damage to the flight muscles. We suggest that nectar feeding, the use of PPP, and intense exercise are causally linked and have allowed the evolution of powerful fliers that feed on nectar., (Copyright © 2017, American Association for the Advancement of Science.)

The genomic basis of the response to dietary intervention of human gut beneficial bacteria remains elusive, which hinders precise manipulation of the microbiota for human health. After receiving a dietary intervention enriched with nondigestible carbohydrates for 105 days, a genetically obese child with Prader-Willi syndrome lost 18.4% of his body weight and showed significant improvement in his bioclinical parameters. We obtained five isolates (C1, C15, C55, C62, and C95) of one of the most abundantly promoted beneficial species, Bifidobacterium pseudocatenulatum , from a postintervention fecal sample. Intriguingly, these five B. pseudocatenulatum strains showed differential responses during the dietary intervention. Two strains were largely unaffected, while the other three were promoted to different extents by the changes in dietary carbohydrate resources. The differential responses of these strains were consistent with their functional clustering based on the COGs (Clusters of Orthologous Groups), including those involved with the ABC-type sugar transport systems, suggesting that the strain-specific genomic variations may have contributed to the niche adaption. Particularly, B. pseudocatenulatum C15, which had the most diverse types and highest gene copy numbers of carbohydrate-active enzymes targeting plant polysaccharides, had the highest abundance after the dietary intervention. These studies show the importance of understanding genomic diversity of specific members of the gut microbiota if precise nutrition approaches are to be realized. IMPORTANCE The manipulation of the gut microbiota via dietary approaches is a promising option for improving human health. Our findings showed differential responses of multiple B. pseudocatenulatum strains isolated from the same habitat to the dietary intervention, as well as strain-specific correlations with bioclinical parameters of the host. The comparative genomics revealed a genome-level microdiversity of related functional genes, which may have contributed to these differences. These results highlight the necessity of understanding strain-level differences if precise manipulation of gut microbiota through dietary approaches is to be realized., (Copyright © 2017 Wu et al.)

The incidence of food allergy has increased dramatically in the last few decades in westernized developed countries. We propose that the Western lifestyle and diet promote innate danger signals and immune responses through production of "alarmins." Alarmins are endogenous molecules secreted from cells undergoing nonprogrammed cell death that signal tissue and cell damage. High molecular group S (HMGB1) is a major alarmin that binds to the receptor for advanced glycation end-products (RAGE). Advanced glycation end-products (AGEs) are also present in foods. We propose the "false alarm" hypothesis, in which AGEs that are present in or formed from the food in our diet are predisposing to food allergy. The Western diet is high in AGEs, which are derived from cooked meat, oils, and cheese. AGEs are also formed in the presence of a high concentration of sugars. We propose that a diet high in AGEs and AGE-forming sugars results in misinterpretation of a threat from dietary allergens, promoting the development of food allergy. AGEs and other alarmins inadvertently prime innate signaling through multiple mechanisms, resulting in the development of allergic phenotypes. Current hypotheses and models of food allergy do not adequately explain the dramatic increase in food allergy in Western countries. Dietary AGEs and AGE-forming sugars might be the missing link, a hypothesis supported by a number of convincing epidemiologic and experimental observations, as discussed in this article., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The "Salt Hypothesis" is the notion that an increase in salt intake will increase blood pressure and thus increase the risk of cardiovascular disease (CVD),which has been a point of contention for decades. Despite this, numerous health organizations, dietary guidelines, and government policies advocate population-wide salt restriction. However, there is no conclusive proof that restricting salt intake reduces the risk of hypertension (HTN) and/or CVD events; sodium restriction in fact may paradoxically lead to adverse health outcomes. Importantly, another white crystal, sucrose (or table sugar) but also high-fructose corn syrup are much more detrimental food additives. Indeed, added sugars have the ability to induce hypertension via the promotion of inflammation, oxidative stress, insulin resistance, and obesity. Considering that there is no physiologic requirement for dietary carbohydrate, there is little reason to suspect adverse health consequences from cutting back on sugar. This paper reviews the evidence relating to salt and sugar on HTN and CVD. Based on our review of the scientific literature, guidelines should focus more on reducing sugar rather than salt for the prevention and treatment of HTN and its consequences., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Several recent studies have shown that post-oral sugar sensing rapidly stimulates ingestion. Here, we explored the specificity with which early-phase post-oral sugar sensing influenced ingestive motivation. In experiment 1 , rats were trained to associate the consumption of 0.3 M sucrose with injections of LiCl (3.0 meq/kg ip, conditioned taste aversion) or given equivalent exposures to the stimuli, but in an unpaired fashion. Then, all rats were subjected to two brief-access tests to assess appetitive and consummatory responses to the taste properties of sucrose (0.01-1.0 M), 0.12 M NaCl, and dH 2 O (in 10-s trials in randomized blocks). Intraduodenal infusions of either 0.3 M sucrose or equiosmolar 0.15 M NaCl (3.0 ml) were administered, beginning just before each test. For unpaired rats, intraduodenal sucrose specifically enhanced licking for 0.03-1.0 M sucrose, with no effect on trial initiation, relative to intraduodenal NaCl. Rats with an aversion to sucrose suppressed licking responses to sucrose in a concentration-dependent manner, as expected, but the intraduodenal sucrose preload did not appear to further influence licking responses; instead, intraduodenal sucrose attenuated trial initiation. Using a serial taste reactivity (TR) paradigm, however, experiment 2 demonstrated that intraduodenal sucrose preloads suppressed ingestive oromotor responses to intraorally delivered sucrose in rats with a sucrose aversion. Finally, experiment 3 showed that intraduodenal sucrose preloads enhanced preferential licking to some representative tastants tested (sucrose, Polycose, and Intralipid), but not others (NaCl, quinine). Together, the results suggest that the early phase-reinforcing efficacy of post-oral sugar is dependent on the sensory and motivational properties of the ingesta., (Copyright © 2016 the American Physiological Society.)

The importance of nutrient induced gut-brain signalling in the regulation of human food intake has become an increasing focus of research. Much of the caloric excess consumed comes from dietary sugars, but our knowledge about the mechanisms mediating the physiological and appetitive effects of sweet tastants in the human gut and gut-brain axis is far from complete. The comparative effects of natural sugars vs low calorie sweeteners are also poorly understood. Research in animal and cellular models has suggested a key functional role in gut endocrine cells for the sweet taste receptors previously well described in oral taste. However human studies to date have very consistently failed to show that activation of the sweet taste receptor by low calorie sweeteners placed in the human gut fails to replicate any of the effects on gastric motility, gut hormones or appetitive responses evoked by caloric sugars., (Copyright © 2016. Published by Elsevier Inc.)

Digestive physiology is important for understanding the feeding behaviour of organisms. Specifically, studies on the digestive physiology of frugivorous and nectarivorous birds are important for elucidating their preference patterns in the wild and the selective pressures they exert on fruit pulp and nectar. In this study, digesta transit times and digestive efficiencies of three species of birds, the Cape white-eyes (Zosterops virens), red-winged starlings (Onychognathus morio) and speckled mousebirds (Colius striatus) were investigated on equicaloric glucose or sucrose artificial fruit diets. Three concentrations, approximating the natural range of sugar concentrations in sugary, bird-dispersed fruits were used: low (6.6%), medium (12.4%) and high (22%). Digesta transit times of birds increased with an increase in concentration for all diets but were generally higher on glucose diets. Intake rates, on the other hand, decreased with an increase in sugar concentration. All species of birds failed to maintain a constant assimilated energy intake on glucose diets but mousebirds and white-eyes maintained it on sucrose diets. Apparent assimilation efficiencies of glucose diets for all species were comparable and typical of those found in other frugivorous birds. However, assimilation efficiencies for sucrose diets differed widely with red-winged starlings displaying very low assimilation efficiencies and as a consequence; they lost significant body mass on all sucrose diets. These results demonstrate the importance of digestive physiology in explaining fruit selection patterns in frugivorous birds and how a seemingly trivial physiological trait can have dire ecological consequences., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155μM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30μM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100μM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10μM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous research has shown that both sunflower seed (SF) and sucrose (SC) supplementation can result in variation in milk fat concentration and composition, possibly due to altered fermentation patterns and biohydrogenation of fatty acids in the rumen. The objective of this study was to determine the effects of different sugar concentrations with or without SF supplementation on lactation performance, ruminal fermentation, and milk fatty acid profile in lactating dairy cows. Eight multiparous Holstein dairy cows (body weight=620±15kg, 60±10 d in milk, mean ± standard deviation) were randomly assigned to treatments in a replicated 4×4 Latin square design with a 2×2 factorial arrangement of treatments. Each 21-d period consisted of a 14-d diet adaptation period and 7-d collection period. Dairy cows were fed 1 of the following 4 diets: (1) no additional SC without SF supplementation (NSC-SF), (2) no additional SC with SF supplementation (NSC+SF), (3) SC without SF supplementation (SC-SF), and (4) SC with SF supplementation (SC+SF). The diets contained the same amount of forages (corn silage and alfalfa hay). Four isonitrogenous and isoenergetic diets were formulated by replacing corn grain with SC and SF and balanced using change in proportions of canola meal and sugar beet pulp. No interaction was detected between SC and SF supplementation with respect to dry matter intake, milk yield, and composition. A tendency was found for an interaction between inclusion of SC and SF on energy-corrected milk with the highest amount in the SC-SF diet. Ruminal pH and the molar proportion of acetate were affected by SC inclusion, with an increase related to the SC-SF diet. Diets containing SF decreased the concentrations of short-chain fatty acids (4:0 to 10:0) and medium-chain fatty acids (12:0 to 16:0) in milk fat. The addition of SC tended to decrease the concentration of total trans-18:1. These data provide evidence that exchanging SC for corn at 4% of dietary dry matter influenced milk fat content and rumen pH, resulting in a tendency for decreased concentration of trans-18:1 in milk fat. Sucrose alone did not alter the milk fatty acid profile when cows were fed a combination of unsaturated fat and sugar, although several significant interactions between sugar and unsaturated fat were observed., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Recent findings suggest that the intestinal sodium-glucose transporter 1 (SGLT1) glucose transporter and sensor mediates, in part, the appetite-stimulation actions of intragastric (IG) glucose and nonmetabolizable α-methyl-d-glucopyranoside (MDG) infusions in mice. Here, we investigated the role of SGLT1 in sugar conditioning using SGLT1 knockout (KO) and C57BL/6J wild-type (WT) mice. An initial experiment revealed that both KO and WT mice maintained on a very low-carbohydrate diet display normal preferences for saccharin, which was used in the flavored conditioned stimulus (CS) solutions. In experiment 2, mice were trained to drink one flavored solution (CS+) paired with an IG MDG infusion and a different flavored solution (CS-) paired with IG water infusion. In contrast to WT mice, KO mice decreased rather than increased the intake of the CS+ during training and failed to prefer the CS+ over the CS- in a choice test. In experiment 3, the KO mice also decreased their intake of a CS+ paired with IG glucose and avoided the CS+ in a choice test, unlike WT mice, which preferred the CS+ to CS-. In experiment 4, KO mice, like WT mice preferred a glucose + saccharin solution to a saccharin solution. These findings support the involvement of SGLT1 in post-oral glucose and MDG conditioning. The results also indicate that sugar malabsorption in KO mice has inhibitory effects on sugar intake but does not block their natural preference for sweet taste., (Copyright © 2016 the American Physiological Society.)

It is claimed that sugar consumed in a drink is poorly compensated for by a reduction in subsequent energy intake, however very little research has tested directly the effect on appetite of adding sugar to a drink versus food. In this between subjects study, 144 participants (72 men) consumed preloads sweetened with either sucrose or the low-energy sweetener, sucralose (preload energy difference 162kcal) in the form of a blackcurrant drink, jelly or candy. The different preload viscosities were achieved by varying the amount of thickener (carrageenan) and water in the recipes. Participants completed hunger ratings before and 5, 10 and 20min after consuming their preload. After the 20-minute rating they were served a test-meal comprising an excess of bite-sized sandwiches and a sweet dessert. Energy intake measured for the same meal consumed the previous day (baseline day, no preload consumed) was used in the data analyses to control for individual differences in energy intake. Overall, there was 36% compensation for the energy difference in the preloads, but this did not vary with preload viscosity - if anything compensation was greater for the drink preload, and greater in men. The drink preload also showed an effect of sucrose versus sucralose for hunger. The lack of the predicted effect of viscosity on compensation could not be explained by differences in blood-glucose concentration 20min after the preload (measured in a separate study) or by differences in preload sweetness, flavour intensity, liking or familiarity. Comparison of baseline and test-meal food intakes indicated that, irrespective of energy content, the sweet drinks reduced the relative intake of sweet food. In conclusion, short-term energy compensation did not differ across a set of realistic drink and food stimuli., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The Drosophila mutant tko25t exhibits a deficiency of mitochondrial protein synthesis, leading to a global insufficiency of respiration and oxidative phosphorylation. This entrains an organismal phenotype of developmental delay and sensitivity to seizures induced by mechanical stress. We found that the mutant phenotype is exacerbated in a dose-dependent fashion by high dietary sugar levels. tko25t larvae were found to exhibit severe metabolic abnormalities that were further accentuated by high-sugar diet. These include elevated pyruvate and lactate, decreased ATP and NADPH. Dietary pyruvate or lactate supplementation phenocopied the effects of high sugar. Based on tissue-specific rescue, the crucial tissue in which this metabolic crisis initiates is the gut. It is accompanied by down-regulation of the apparatus of cytosolic protein synthesis and secretion at both the RNA and post-translational levels, including a novel regulation of S6 kinase at the protein level.

Reductions in calorie intake contribute significantly to the positive outcome of bariatric surgeries. However, the physiological mechanisms linking the rerouting of the gastrointestinal tract to reductions in sugar cravings remain uncertain. We show that a duodenal-jejunal bypass (DJB) intervention inhibits maladaptive sweet appetite by acting on dopamine-responsive striatal circuitries. DJB disrupted the ability of recurrent sugar exposure to promote sweet appetite in sated animals, thereby revealing a link between recurrent duodenal sugar influx and maladaptive sweet intake. Unlike ingestion of a low-calorie sweetener, ingestion of sugar was associated with significant dopamine effluxes in the dorsal striatum, with glucose infusions into the duodenum inducing greater striatal dopamine release than equivalent jejunal infusions. Consistently, optogenetic activation of dopamine-excitable cells of the dorsal striatum was sufficient to restore maladaptive sweet appetite in sated DJB mice. Our findings point to a causal link between striatal dopamine signaling and the outcomes of bariatric interventions., (Copyright © 2016 Elsevier Inc. All rights reserved.)