Exploring the Association of Dietary Fructose and Advanced Glycation End Products

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Description
Background: Sugars form advanced glycation end products (AGEs) throughnatural metabolism and interactions with proteins, lipids, and nucleic acids, which accumulate in tissues and have been implicated in the etiology of chronic diseases. Due to the increased consumption of fructose and

Background: Sugars form advanced glycation end products (AGEs) throughnatural metabolism and interactions with proteins, lipids, and nucleic acids, which accumulate in tissues and have been implicated in the etiology of chronic diseases. Due to the increased consumption of fructose and its high ability to form AGEs, a further understanding of this association is important to clarify the role of sugars in disease. The objective was to explore the association between usual fructose intake and serum levels of AGEs, as measured by carboxymethyl-lysine (CML) and methylglyoxal derivative (MG-H1), in healthy adults. Methods: This is a secondary analysis of a 15-d controlled feeding study (n=100) with participants consuming their usual diet conducted in the Phoenix metropolitan area. To assess participants’ usual diet, they were asked to complete two 7-d food diaries, which were then used to create custom 15-d menu plans administered during the feeding period. Forty participants were selected based on their 15-d mean total fructose intake for this analysis [top and bottom 20% of the sample distribution (median, IQR); high fructose (HF) n= 20, 72.6 (66.1-90.4) g/day, low fructose (LF) n= 20, 28.8 (22.7-32.2) g/day. Fasting serum collected five weeks after the feeding period were analyzed for CML and MG-H1, two well-established AGEs, using ELISA kits. A database of 549 common foods with known CML amounts was used to calculate exogenous CML intake based on daily food intake data. A general linear model was fitted to investigate the difference in serum CML and MG-H1 between LF and HF groups while adjusting for age, gender, BMI, and exogenous CML intake. Results: Participants in the HF group had significantly higher serum CML and lower MG-H1 levels compared to participants in the LF group (p=0.013 and p=0.002, respectively). This difference remained statistically significant after adjusting for covariates. Conclusions: The findings suggest that endogenous CML formation may be an explanation for the significantly higher serum CML levels in the HF compared to the LF group. This is significant in further understanding mechanisms of fructose intake and disease etiology and could have implications for at-risk populations consuming a high fructose diet.
Date Created
2021
Agent

Intermittent Fasting Regimens have a Limited Effect on Circulating Markers of Oxidative Stress in Overweight/Obese Individuals: A Systematic Review of Randomized Controlled Trials

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Description

Background: The US population faces a continual increase in obesity prevalence, raising health concerns due to associated comorbidities ranked as leading causes of preventable, premature death world-wide. Scientists have found a link between obesity-associated conditions and oxidative stress (OS). To

Background: The US population faces a continual increase in obesity prevalence, raising health concerns due to associated comorbidities ranked as leading causes of preventable, premature death world-wide. Scientists have found a link between obesity-associated conditions and oxidative stress (OS). To date, renewed interest in the effectiveness of dietary regimens in decreasing body weight is a popular research topic. Intermittent fasting (IF) is a popular and promising weight management strategy. To date, there have been no systematic reviews examining whether IF can reduce oxidative stress in overweight/obese adults. <br/><br/>Objective: Conduct a systematic review to evaluate the effects of intermittent fasting (IF) regimens on circulating markers of oxidative stress in overweight/obese adults compared to continuous calorie restriction (CR). <br/><br/>Methods: Databases PubMed, SCOPUS, ProQuest, and Cochrane were searched on February 21, 2021 for eligible articles limiting selection to those in the English language. Predefined search terms and restrictions were applied by two of the authors conducting the search. References from articles generated were also considered. Selected articles were limited to randomized controlled trials (RCTs) and human trials evaluating the effects of intermittent fasting (IF) dietary regimens in comparison to continuous calorie restriction (CR). Study populations considered were limited to those within the range of 18-65 years having a body mass index (BMI) of ≥25 kg/m2 and in otherwise generally good health with the absence of pre-existing acute or chronic conditions. The Academy of Nutrition and Dietetics Evidence Analysis Library Quality Rating Worksheet was used to assess the methodological quality of each of the studies and the Academy of Nutrition and Dietetics Grade Definitions and Conclusion Grading Table were used to appraise the quality of evidence.<br/><br/>Results: Six articles met eligibility criteria and were included in this review. Cumulatively 355 overweight/obese participants were assessed. Quality ratings performed by two of the authors revealed a high-quality rating for all six of the articles. One of the articles reported a significant IF associated difference in circulating 8-isoprostane concentrations and another article reported a significant decrease in circulating oxidative lipoproteins concentrations. The remaining articles showed no significant difference on OS markers following IF. <br/><br/>Conclusions: Based on the six articles included in this systematic review, IF was concluded to have limited impact on reducing circulating markers of OS in overweight/obese adults. Overall, the evidence was heterogeneous in relation to IF interventions and outcomes precluding a meta-analysis. Consequently, evidence to make dietary recommendations for reducing oxidative stress with IF interventions is insufficient at this point.

Date Created
2021-05
Agent

The Impact of Different Normalization Methods on Western Blot Results

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Description

Reducing the amount of error and introduced data variability increases the accuracy of Western blot results. In this study, different methods of normalization for loading differences and data alignment were explored with respect to their impact on Western blot results.

Reducing the amount of error and introduced data variability increases the accuracy of Western blot results. In this study, different methods of normalization for loading differences and data alignment were explored with respect to their impact on Western blot results. GAPDH was compared to the LI-COR Revert total protein stain as a loading control. The impact of normalizing data to a control condition, which is commonly done to align Western blot data distributed over several immunoblots, was also investigated. Specifically, this study addressed whether normalization to a small subset of distinct controls on each immunoblot increases pooled data variability compared to a larger set of controls. Protein expression data for NOX-2 and SOD-2 from a study investigating the protective role of the bradykinin type 1 receptor in angiotensin-II induced left ventricle remodeling were used to address these questions but are also discussed in the context of the original study. The comparison of GAPDH and Revert total protein stain as a loading control was done by assessing their correlation and comparing how they affected protein expression results. Additionally, the impact of treatment on GAPDH was investigated. To assess how normalization to different combinations of controls influences data variability, protein data were normalized to the average of 5 controls, the average of 2 controls, or an average vehicle and the results by treatment were compared. The results of this study demonstrated that GAPDH expression is not affected by angiotensin-II or bradykinin type 1 receptor antagonist R-954 and is a less sensitive loading control compared to Revert total protein stain. Normalization to the average of 5 controls tended to reduce pooled data variability compared to 2 controls. Lastly, the results of this study provided preliminary evidence that R-954 does not alter the expression of NOX-2 or SOD-2 to an expression profile that would be expected to explain the protection it confers against Ang-II induced left ventricle remodeling.

Date Created
2021-05
Agent

Fetal Growth Models of Cardiac Size and Function, and Prediction of Congenital Cardiomyopathy in Fetuses with Diabetic Mothers

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Description

2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without

2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing fetal heart development but they warrant revalidation and adjustment. 377 normal fetuses with healthy mothers, 98 normal fetuses with diabetic mothers, and 37 fetuses with cardiomyopathy and diabetic mothers had their cardiac structural dimensions, cardiothoracic ratio, valve flow velocities, and heart rates measured by fetal ECHO in a retrospective chart review. Cardiac features were fitted to linear functions, with respect to gestational age, femur length, head circumference, and biparietal diameter and z-scores were created to model normal fetal growth for all parameters. These z-scores were used to assess what metrics had no difference in means between the normal fetuses of both healthy and diabetic mothers but differed from those diagnosed with cardiomyopathy. It was found that functional metrics like mitral and tricuspid E wave and pulmonary velocity could be important predictors for cardiomyopathy when fitted by gestational age, femur length, head circumference, and biparietal diameter. Additionally, aortic and tricuspid annulus diameters when fitted to estimated gestational age showed potential to be predictors for fetal cardiomyopathy. While the metrics overlapped over their full range, combining them together may have the potential for predicting cardiomyopathy in utero. Future directions of this study will explore creating a classifier model that can predict cardiomyopathy using the metrics assessed in this study.

Date Created
2021-05
Agent

Fetal Growth Models of Cardiac Size and Function, and Prediction of Congenital Cardiomyopathy in Fetuses with Diabetic Mothers

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Description

2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without

2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing fetal heart development but they warrant revalidation and adjustment. 377 normal fetuses with healthy mothers, 98 normal fetuses with diabetic mothers, and 37 fetuses with cardiomyopathy and diabetic mothers had their cardiac structural dimensions, cardiothoracic ratio, valve flow velocities, and heart rates measured by fetal ECHO in a retrospective chart review. Cardiac features were fitted to linear functions, with respect to gestational age, femur length, head circumference, and biparietal diameter and z-scores were created to model normal fetal growth for all parameters. These z-scores were used to assess what metrics had no difference in means between the normal fetuses of both healthy and diabetic mothers, but differed from those diagnosed with cardiomyopathy. It was found that functional metrics like mitral and tricuspid E wave and pulmonary velocity could be important predictors for cardiomyopathy when fitted by gestational age, femur length, head circumference, and biparietal diameter. Additionally, aortic and tricuspid annulus diameters when fitted to estimated gestational age showed potential to be predictors for fetal cardiomyopathy. While the metrics overlapped over their full range, combining them together may have the potential for predicting cardiomyopathy in utero. Future directions of this study will explore creating a classifier model that can predict cardiomyopathy using the metrics assessed in this study.

Date Created
2021-05
Agent

Modifications of the urinary metabolome in college students after 4-weeks of daily vinegar ingestion that resulted in reductions in depression scores

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Description

Depression is a worldwide public health problem that affects millions of people every year. Due to recent reports that depressed individuals have an altered gut microbiome composition, there is speculation that treatments that influence microorganisms in the gut could potentially

Depression is a worldwide public health problem that affects millions of people every year. Due to recent reports that depressed individuals have an altered gut microbiome composition, there is speculation that treatments that influence microorganisms in the gut could potentially lead to alleviation of depressive symptoms. Apple cider vinegar has been studied extensively for its health-promoting properties and benefits. Apple cider vinegar’s main ingredient is the short chain fatty acid, acetic acid. Short chain fatty acids have been shown to improve mood state and depressive symptoms, as well as amplify the effect of prebiotics in restoring the gut microbiome. This experimental design study examined the effects of ingesting 2 tbsp. apple cider vinegar (1 g acetic acid) twice daily with a meal on the levels of urinary metabolites in 14 college students compared to a control group of 11 college students that took one vinegar supplement tablet (0.015 g of acetic acid) daily for 28 days. All participants were healthy, normal to underactive (< 300 minutes of moderate exercise a week), and free of chronic or acute illnesses. Urinary metabolite analysis revealed a significant production of enzymes involved in the hexosamine pathway in the liquid vinegar group compared to baseline levels. However, anticipation of an alteration in tryptophan metabolites, a possible consequence of altered metabolism of gut microflora, was not observed. These data suggest that apple cider vinegar might be a potential treatment for depression through the production of hexosamine pathway enzymes.

Date Created
2021-05
Agent

Targeted Metabolomics Reveals the Effect of Nitrate Supplementation on Vascular Function

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Description
In the United States, two-thirds of adults are considered hypertensive orprehypertensive. In addition, chronic illness, such as hypertension, cardiovascular disease, and type II diabetes, results in $3.5 trillion in annual healthcare cost and is the primary cause of disability and

In the United States, two-thirds of adults are considered hypertensive orprehypertensive. In addition, chronic illness, such as hypertension, cardiovascular disease, and type II diabetes, results in $3.5 trillion in annual healthcare cost and is the primary cause of disability and death. As a result, many individuals seek cheaper and simpler alternatives to combat their conditions. In this exploratory analysis, a study assessing nitrate intake and its effects on vascular function in 39 young adult males was investigated for underlying metabolic variations through a liquid chromatography – mass spectrometry-based large-scale targeted metabolomics approach. A two-way repeated measures ANOVA was used, and 18 significant metabolites were discovered across the time, treatment, and time & treatment groups, including prostaglandin E2 (p<0.001), stearic acid (p=0.002), caprylic acid (p=0.016), pentadecanoic acid (p=0.027), and heptadecanoic acid (p=0.005). In addition, log-transformed principal component analysis and orthogonal partial least squares – discriminant analysis models demonstrated distinct separation among the treatment, control, and time variables. Moreover, pathway and enrichment analyses validated the effect of nitrate intake on the metabolite sets and its possible function in fatty acid oxidation. This better understanding of altered metabolic pathways may help explicate the benefits of nitrate on vascular function and reveal any unknown mechanisms of its supplementation.
Date Created
2020
Agent

Meal-time Matters: An 8-week Randomized Control Trial to Examine the Effects of a Daily 18-hour Fast on Diet Quality in College Students

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Description
ABSTRACT

Background. College students’ modifiable health behaviors, including unhealthful eating patterns, predispose them to risk for future cardiometabolic conditions.

Purpose. This novel 8-week randomized control parallel-arm study compared the effects of a daily 18-hour Time-Restricted Feeding protocol vs. an 8-hour fast

ABSTRACT

Background. College students’ modifiable health behaviors, including unhealthful eating patterns, predispose them to risk for future cardiometabolic conditions.

Purpose. This novel 8-week randomized control parallel-arm study compared the effects of a daily 18-hour Time-Restricted Feeding protocol vs. an 8-hour fast on diet quality in college students. Secondary outcomes were resting morning blood pressure, biomarkers of glucose regulation, biomarkers of lipid metabolism, and anthropometric measures.

Methods. Eighteen healthy college students (age = 23 ± 4 years; BMI = 23.2 ± 2.3 kg/m2; MET = 58.8 ± 32.9 min/wk) completed this study. Participants were randomized to a daily 18-hour fasting protocol (Intervention; n = 8) or a daily 8-hour fasting protocol (Control; n = 10) for eight weeks. One ‘cheat’ day was permitted each week. Outcomes were measured at weeks 0 (baseline), 4, and 8. A non-parametric Mann Whitney U test was used to compare the week 4 change from baseline between groups. Statistical significance was set at p≤0.05.

Results. Diet quality (p = 0.030) and body weight (p = 0.016) improved from baseline to week 4 for the INV group in comparison to the CON group. The data suggest these improvements may be related to reductions in snacking frequency and increased breakfast consumption. Fasting blood glucose and hip circumference tended to improve for the INV group in comparison to the CON group (p = 0.091 and p = 0.100). However, saturated fat intake tended to increase in the INV group in comparison to the CON group (p = 0.064). Finally, there were no treatment differences between groups (p>0.05) for the 4-week change in total calories, dietary vitamin C, added sugars, resting systolic blood pressure, resting diastolic blood pressure, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, waist circumference, or MET.

Conclusion. These data, although preliminary, suggest that the 18-hour fasting protocol was effective for improving diet quality and reducing weight in comparison to the 8-hour fasting protocol in healthy college students. Future intervention trials will need to confirm these findings and determine the long-term relevance of these improvements for health outcomes.
Date Created
2020
Agent

The Effect of Glucocorticoids on Insulin Resistance in Rat Skeletal Muscle via TXNIP

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Description
Glucocorticoids are a class of corticosteroids that bind to glucocorticoid receptors
within cells that result in changes in the metabolism of carbohydrates and immune functions.
Ingesting glucocorticoids has also been linked to insulin resistance, a main feature of Type 2

Glucocorticoids are a class of corticosteroids that bind to glucocorticoid receptors
within cells that result in changes in the metabolism of carbohydrates and immune functions.
Ingesting glucocorticoids has also been linked to insulin resistance, a main feature of Type 2
diabetes. Experiments including polymerase chain reaction, western blotting, and glycogen
synthase analysis were conducted to determine if exposure to higher doses of dexamethasone, a
glucocorticoid, induces insulin resistance in cultured rat skeletal muscle via interaction with
thioredoxin-interacting protein (TXNIP). Treatment with dexamethasone was shown to cause
mild increases in TXNIP while a definitive increase or decrease in insulin signaling was unable
to be determined.
Date Created
2020-05
Agent

Effects of an Urban Diet on Glucose, Sodium, and Osmolality in the Mourning Dove, Zenaida macroura

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Description
Prior studies of Mourning Doves have observed no changed in glucose in response to either a high fat “chow” diet or a white bread diet. In the current feeding study, we fed doves an urban diet, high in carbohydrates, fat,

Prior studies of Mourning Doves have observed no changed in glucose in response to either a high fat “chow” diet or a white bread diet. In the current feeding study, we fed doves an urban diet, high in carbohydrates, fat, and sodium, which is representative of typical American nutrition accessible to the avian population in an urbanized environment. Based on studies of other avian species that examined the effects of an urban diet on physiology, I hypothesized that doves fed an urban diet would have increased plasma glucose and sodium, which would promote an increase in plasma osmolality. This hypothesis was based on preliminary data that found birds fed an urban diet developed impaired vasodilation compared to seed diet control birds. Therefore, differences in plasma glucose, sodium, and osmolality were examined as increases may contribute to the impairment. Adult doves of both sexes were captured on the Arizona State University, Tempe campus. Doves were placed in two dietary groups: an urban diet consisting of a 50/50 ratio of French fries and nutritionally-balanced bird seed (n=7) and a control group of only the seed diet (n=6). Following the four-week diets, birds were euthanized, and cardiac plasma samples were collected from birds to measure glucose, sodium, and osmolality. There were no significant differences between the two study groups in plasma glucose concentration (p=0.445), sodium concentration (p=0.731), or osmolality (p=0.692). Sodium concentrations were signficantly more variable in birds consuming a seed diet than those that were provided the mixed French fry and seed diet (p=0.014). These results suggest that glucose, sodium, and osmolality likely do not contribute to the altered vasodilation of doves fed an urban diet and that such a diet may not be as detrimental to the doves health given their phenotypic flexibility.
Date Created
2020-05
Agent