Source of dietary sucrose influences development of leptin resistance in male and female rats.

Male rats offered 30% sucrose solution in addition to chow develop leptin resistance without an increase in energy intake or body fat. This study tested whether the leptin resistance was dependent on the physical form of the sucrose. Sprague-Dawley rats were offered a sucrose-free (NS) diet, a 66.6% of energy as sucrose (HS) diet, or the NS diet + 30% sucrose solution (LS). Sucrose intake of LS rats equaled that of HS rats, but total carbohydrate intake exceeded that of HS rats. After 33 days, male and female LS rats were resistant to the inhibitory effect of peripherally administered leptin on food intake. LS rats drank small, frequent meals of sucrose during light and dark periods, whereas HS rats consumed more meals during the dark than the light period and remained responsive to leptin. Diet did not affect daily energy intake or insulin sensitivity. There was a small increase in body fat in the female rats. Leptin sensitivity was restored within 5 days of withdrawal from sucrose in male LS rats. This rapid reversal suggested that leptin resistance was associated with the metabolic impact of drinking sucrose. An experiment was carried out to test whether activity of the hexosamine biosynthetic pathway and glycation of leptin signaling proteins were increased in LS rats, but the results were equivocal. A final experiment determined that female LS rats were leptin-resistant within 18 days of access to sucrose solution and that the small, but significant, increase in body fat was associated with increased adipocyte glucose utilization and insulin responsiveness, which may have been secondary to adipocyte leptin resistance.

Evaluation of a novel biomarker of added sugar intake (δ 13C) compared with self-reported added sugar intake and the Healthy Eating Index-2010 in a community-based, rural U.S. sample.

OBJECTIVE: The δ 13C value of human blood is an emerging novel biomarker of added sugar (AS) intake for adults. However, no free-living, community-based assessments of comparative validity of this biomarker have been conducted. The purpose of the present investigation was to determine if Healthy Eating Index-2010 (HEI-2010) score, SoFAAS score (HEI-2010 sub-component for solid fat, alcohol and AS), AS and sugar-sweetened beverage (SSB) intakes were associated with δ 13C value of fingerstick blood in a community-based sample of adults, while controlling for relevant demographics. DESIGN: A cross-sectional analysis of data obtained from assessments of BMI, dietary intake using 24 h recalls and a fingerstick blood sample was completed. Statistical analyses included descriptive statistics, multiple linear regression and one-way ANOVA. SETTING: Rural Southwest Virginia, U.S.A. SUBJECTS: Adults (n 216) aged >18 years who consumed at least 837 kJ/d (200 kcal/d) from SSB. RESULTS: This sample of adult participants with low socio-economic status demonstrated a mean HEI-2010 score of 43.4 (sd 12.2), mean SoFAAS score of 10.2 (sd 5.7), mean AS intake of 93 (sd 65) g/d and mean blood δ 13C value of -18.88 (sd 0.7) ‰. In four separate regression models, HEI-2010 (R 2=0.16), SoFAAS (R 2=0.19), AS (R 2=0.15) and SSB (R 2=0.14) predicted δ 13C value (all P≤0.001). Age was also predictive of δ 13C value, but not sex or race. CONCLUSIONS: These findings suggest that fingerstick δ 13C value has the potential to be a minimally invasive method for assessing AS and SSB intake and overall dietary quality in community-based settings. Strengths, limitations and future areas of research for using an objective δ 13C biomarker in diet-related public health studies are discussed.

Sugar-containing beverage intake at the age of 1 year and cardiometabolic health at the age of 6 years: the Generation R Study.

BACKGROUND: Consumption of sugar-containing beverages (SCBs) in adults has been associated with an increased risk of metabolic syndrome. Although the effect of SCB on body weight in children is well established, little is known about the cardiometabolic effects in young children. We studied the associations of SCB intake at the age of 1 year with cardiometabolic health at age 6 years. METHODS: This study was performed among 2,045 Dutch children from a population based prospective birth cohort. SCB intake was assessed with a semi-quantitative food frequency questionnaire at the age of 13 months and sex-specific tertiles were created. Children visited the research center at the age of 6 years. We created a continuous cardiometabolic risk factor score including: body fat percentage, blood pressure, insulin, HDL-cholesterol and triglycerides. Age-and sex-specific standard deviation (SD) scores were created for all outcomes. Multivariable linear regression was performed with adjustment for socio-demographic and lifestyle variables of mother and child. RESULTS: In the total population, we observed an association between higher SCB intake at 13 months of age and a higher cardiometabolic risk factor score at the age of 6 years (0.13SD (95 % CI 0.01; 0.25), highest vs. lowest tertile) After stratification by sex, we found that boys in the highest tertile of SCB intake had a higher cardiometabolic risk factor score (0.18 SD (95 % CI 0.01; 0.34)), as compared to boys in the lowest tertile of SCB intake. There was no significant association in girls. We did not find associations of SCB intake with the individual cardiometabolic risk factors in the total population, or in the stratified analyses. CONCLUSION: Higher SCB intake at 1 year of age was associated with a higher cardiometabolic risk factor score at age 6 years in boys, but not in girls. Further research on sex-specific effects of SCBs is needed.

Combined high-fat diet and sustained high sucrose consumption promotes NAFLD in a murine model.

BACKGROUND: The study of NAFLD in humans has several limitations. Using murine models helps to understand disease pathogenesis. AIM: Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. MATERIAL AND METHODS: Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 3) High-fat cornstarch diet (HFCO) + 5% sucrose in drinking water. 4) Chow diet + 20% sucrose in drinking water (HSD). Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. RESULTS: The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). Liver weight TG and colesterol concentrations in liver were greater in the HFC diet. There were no increased levels of iron in the liver. Rats in HFC gained significantly more weight (P < 0.001). All experimental groups showed fasting hyperglycemia. HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). The HSD and the HFCO diets developed also hyperglycemia. HSD had significantly higher fasting hyperinsulinemia. Serum leptin was higher in the HFC diet (p = 0.001). In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only.

Influencia de la dieta sobre las actividades de fosforiladoras de glucosa en hígado e intestino de rata / Influence of diet on glucose phosphorylating activity of rat liver and small intestine

La fosforilación de la glucosa en los mamíferos, es catalizada por una familia de isoenzimas (hexoquinasas I-IV; HQ) de diferente Km para el azúcar. En los hepatocitos y células b-pancreáticas se encuentra la glucoquinasa (GQ; HQ IV) de Km elevado (12-20 mM). Hemos observado que GQ está presente en el intestino delgado y podría contribuir a la producción de lactato durante la absorción del azúcar. En este trabajo se determinó el efecto de la dieta (ratarina R; 60% de glucosa G; sacarosa S; almidón A; caseína C), suministrada ad libitum, sobre las actividades de HQ y GQ en homogenatos de hígado y mucosa intestinal de rata. El suministro de glucosa (5%) en el agua de beber (SG) también fue evaluado en las dietas con R y G. Las actividades de HQ (Glucosa 1 mM) y la capacidad fosforilativa total (CFT: Glucosa = 100 mM) se determinaron enzimáticamente. GQ se estimó por diferencia. En el grupo control (R) y en S, A y C, la GQ hepática fue un 85% de la CFT, mientras que en G, GSG y RSG un 66%. La HQ intestinal alcanzó en los grupos R, GSG, A y C un 87% y en RSG un 30% de la CFT. La GQ en G, S, aumentó, pero una menor magnitud. La presencia de GQ en el intestino delgado y su expresión diferencial de acuerdo a la dieta, abren la posibilidad de que dicho órgano contribuya al metabolismo inicial de la glucosa procedente de la dieta y provea al hígado de un precursor (lactato) muy eficaz para sus procesos anabólicos.

Glucose phosphorylation in mammals, is catalyzed by a family of isoenzymes (hexokinases I- IV; HQ) of different Km for the sugar. In hepatocytes and pancreatic b- cells are glucokinase (GQ ; HQ IV) of high Km (12-20 mM). We observed that GQ is present in the small intestine and may contribute to the production of lactate during the absorption of sugar. In this work, the effect of diet (ratarina R, G 60% glucose, sucrose S; starch A; casein C) provided ad libitum , on the activities of HQ and GQ in liver homogenates of rat intestinal mucosa . The supply of glucose (5%) in the drinking water ( SG ) was also evaluated in the diets with R and G. HQ activities (Glucose 1 mM) and phosphorylating full capacity ( CFT : Glucose = 100 mM ) were determined enzymatically . GQ was estimated by difference. In the control group (R) and S, A and C, the GQ liver was about 85% of CFT, whereas G, GSG and RSG 66%. The intestinal HQ reached in the R groups, GSG, A and C by 87% and 30% RSG the CFT. The GQ in G, S , increased , but a lower magnitude. the presence of glucokinase in the small intestine and its differential expression according to diet, open the possibility that this structure contributes to initial metabolism of glucose and provide to the liver a precursor (lactate) very effective for their anabolic processes.

Association of δ¹³C in fingerstick blood with added-sugar and sugar-sweetened beverage intake.

A reliance on self-reported dietary intake measures is a common research limitation, thus the need for dietary biomarkers. Added-sugar intake may play a role in the development and progression of obesity and related comorbidities; common sweeteners include corn and sugar cane derivatives. These plants contain a high amount of ¹³C, a naturally occurring stable carbon isotope. Consumption of these sweeteners, of which sugar-sweetened beverages are the primary dietary source, might be reflected in the δ¹³C value of blood. Fingerstick blood represents an ideal substrate for bioassay because of its ease of acquisition. The objective of this investigation was to determine if the δ¹³C value of fingerstick blood is a potential biomarker of added-sugar and sugar-sweetened beverage intake. Individuals aged 21 years and older (n = 60) were recruited to attend three laboratory visits; assessments completed at each visit depended upon a randomly assigned sequence (sequence one or two). The initial visit included assessment of height, weight, and dietary intake (sequence one: beverage intake questionnaire, sequence two: 4-day food intake record). Sequence one participants completed a food intake record at visit two, and nonfasting blood samples were obtained via routine fingersticks at visits one and three. Sequence two participants completed a beverage intake questionnaire at visit two, and provided fingerstick blood samples at visits two and three. Samples were analyzed for δ¹³C value using natural abundance stable isotope mass spectrometry. δ¹³C value was compared to dietary outcomes in all participants, as well as among those in the highest and lowest tertile of added-sugar intake. Reported mean added-sugar consumption was 66 ± 5 g/day, and sugar-sweetened beverage consumption was 330 ± 53 g/day and 134 ± 25 kcal/day. Mean fingerstick δ¹³C value was -19.94‰ ± 0.10‰, which differed by body mass index status. δ¹³C value was associated (all P < 0.05) with intake of total added sugars (g, r = 0.37; kcal, r = 0.37), soft drinks (g, r = 0.26; kcal, r = 0.27), and total sugar-sweetened beverage (g, r = 0.28; kcal, r = 0.35). The δ¹³C value in the lowest and the highest added-sugar intake tertiles were significantly different (mean difference = -0.48‰; P = 0.028). Although there are several potential dietary sources for blood carbon, the δ¹³C value of fingerstick blood shows promise as a noninvasive biomarker of added-sugar and sugar-sweetened beverage intake based on these findings.

A free-choice high-fat high-sugar diet induces glucose intolerance and insulin unresponsiveness to a glucose load not explained by obesity.

OBJECTIVES: In diet-induced obesity, it is not clear whether impaired glucose metabolism is caused directly by the diet, or indirectly via obesity. This study examined the effects of different free-choice, high-caloric, obesity-inducing diets on glucose metabolism. In these free-choice diets, saturated fat and/or a 30% sugar solution are provided in an addition to normal chow pellets. METHOD: In the first experiment, male rats received a free-choice high-fat high-sugar (HFHS), free-choice high-fat (HF) or a chow diet. In a second experiment, male rats received a free-choice high-sugar (HS) diet or chow diet. For both experiments, after weeks 1 and 4, an intravenous glucose tolerance test was performed. RESULTS: Both the HFHS and HF diets resulted in obesity with comparable plasma concentrations of free fatty acids. Interestingly, the HF diet did not affect glucose metabolism, whereas the HFHS diet resulted in hyperglycemia, hyperinsulinemia and in glucose intolerance because of a diminished insulin response. Moreover, adiposity in rats on the HF diet correlated positively with the insulin response to the glucose load, whereas adiposity in rats on the HFHS diet showed a negative correlation. In addition, total caloric intake did not explain differences in glucose tolerance. To test whether sugar itself was crucial, we next performed a similar experiment in rats on the HS diet. Rats consumed three times as much sugar when compared with rats on the HFHS diet, which resulted in obesity with basal hyperinsulinemia. Glucose tolerance, however, was not affected. CONCLUSION: Together, these results suggest that not only obesity or total caloric intake, but the diet content also is crucial for the glucose intolerance that we observed in rats on the HFHS diet.

Evaluation of a novel isotope biomarker for dietary consumption of sweets.

Carbon isotopic signatures ("δ¹³C") might reflect consumption of corn- and cane-based sweeteners. The authors hypothesized that the δ¹³C value of human serum is higher for individuals with high versus low intakes of corn- and cane-based sweeteners (measured as sweetened beverage intake). They conducted a cross-sectional study within the Atherosclerosis Risk in Communities Magnetic Resonance Imaging study (Maryland, 2005-2006). Diet was assessed by food frequency questionnaire, and blinded serum samples were assayed by natural abundance stable isotope mass spectroscopy. Studied were 186 participants (53% male; mean age, 71 years; mean body mass index, 30 kg/m²). Serum δ¹³C values for individuals with high sweetened beverage intakes were significantly higher than for those with low intakes (-19.15‰ vs. -19.47‰, P < 0.001). Serum δ¹³C value increased 0.20‰ for every serving/day of sweetened beverages (P < 0.01). The association between sweetened beverages and serum δ¹³C value remained significant after adjustment for confounding by corn-based product intake (P < 0.001). Serum δ¹³C values were also associated with waist circumference, body mass index, and waist-to-hip ratio. This study provides the first known evidence that the δ¹³C value of human serum differs between persons consuming low and high amounts of sweets. Within the proper framework, serum δ¹³C value could be developed into an objective biomarker promoting more reliable assessment of dietary sweets intake.

Opposing effects of dietary sugar and saturated fat on cardiovascular risk factors and glucose metabolism in mitochondrially impaired mice.

PURPOSE: Both dietary fat and dietary sucrose are major components of Western diets that may differentially affect the risk for body mass gain, diabetes mellitus, and cardiovascular disease. METHODS: We have phenotypically analyzed mice with ubiquitously impaired expression of mitochondrial frataxin protein that were challenged with diets differing in macronutrient content, namely high-sucrose/low-fat and high-saturated fat/low-sugar diets. RESULTS: We find here that a high-sucrose/low-fat diet has especially detrimental effects in mice with impaired mitochondrial metabolism promoting several independent cardiovascular risk factors, including impaired glucose metabolism, fasting hyperinsulinemia, reduced glucose-stimulated insulin secretion, increased serum triglycerides, and elevated cholesterol levels due to increased expression of HMG-CoA reductase. In contrast, a high-saturated fat/low-sugar diet protects mice with impaired mitochondrial metabolism from diet-induced obesity by increasing total energy expenditure and increasing expression of ACAA2, a rate-limiting enzyme of mitochondrial beta-oxidation, whereas no concomitant improvement of glucose metabolism was observed. CONCLUSIONS: Taken together, our results suggest that mitochondrial dysfunction may cause sucrose to become a multifunctional cardiovascular risk factor, whereas low-sugar diets high in saturated fat may prevent weight gain without improving glucose metabolism.

The natural 13C abundance of plasma glucose is a useful biomarker of recent dietary caloric sweetener intake.

There is a need for objective biomarkers of dietary intake, because self-reporting is often subject to bias. We tested the validity of a biomarker for the fraction of dietary carbohydrate (CHO) from cane sugar and high fructose corn syrup (C(4) sugars) using natural (13)C abundance of plasma glucose. In a randomized, single-blinded, crossover design, 5 participants consumed 3 weight-maintaining diets for 7 d, with a 2-wk washout between diet periods. Diets differed in the fraction of total CHO energy from C(4) sugars (5, 16, or 32%). During each diet period, blood samples were drawn at hours 0800 and 1600 on d 1, 3, and 5 and at 0800, 1000, 1200, 1400, and 1600 on d 7. The delta(13)C abundance of plasma glucose was analyzed via GC- isotope ratio MS. Within each diet period, delta(13)C abundance of the 0800 fasting glucose did not change from baseline with increasing time during a diet period; however, there was a strong positive correlation (R(2) = 0.89) between delta(13)C abundance of the glucose concentration at 1000 on d 7 and the percent of breakfast CHO from C(4) sugars. Also, delta(13)C abundance of the combined plasma glucose samples on d 7 demonstrated a strong positive correlation (R(2) = 0.90) with the percent of total daily CHO from C(4) sugars. The natural delta(13)C abundance of postprandial plasma glucose relative to dietary C(4) CHO content was a valid biomarker for contributions of C(4) caloric sweeteners from the previous meal.

Breakfasts that release glucose at different speeds interact with previous alcohol intake to influence cognition and mood before and after lunch.

Alcohol consumption and the glycemic load (GL) of a meal interact to influence both mood and memory. The authors compared the effects of eating a high GL lunch on mood and memory after consumption of a breakfast high in either rapidly (RAG) or slowly (SAG) available glucose. When less than 4.5 g of alcohol had been drunk the previous evening, the eating of a high RAG meal was associated with better memory later in the morning. In contrast, after more than 4.5 g of alcohol had been drunk the previous evening, the SAG meal resulted in better memory. After lunch, if more than 4.5 g alcohol had been drunk the previous evening, the RAG breakfast, but neither the SAG meal nor fasting, resulted in a more confused feeling.

An analytical method for the quantitation of mannitol and disaccharides in serum: a potentially useful technique in measuring small intestinal permeability in vivo.

An electrochemical-HPLC method for the determination of mannitol and lactulose is presented which may facilitate routine testing of intestinal permeability by requiring only a single blood sample instead of a 6-hour urine collection. Chromatographic conditions are described which allow separation of the closely related sugars lactulose and the dietary disaccharides lactose and sucrose. Preliminary results in normal controls and patients with untreated coeliac disease are presented.