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Novel Organometallic Complex Mitigates Liver Injury caused by a 10-Week High Fat Diet in Adolescent Male Sprague-Dawley Rats

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Nonalcoholic fatty liver disease is the most common form of chronic liver disease in the United States. Diets high in saturated fats are known to promote obesity and hepatic steatosis. The consumption of a high fat diet (HFD) can increase

Nonalcoholic fatty liver disease is the most common form of chronic liver disease in the United States. Diets high in saturated fats are known to promote obesity and hepatic steatosis. The consumption of a high fat diet (HFD) can increase the risk factors associated with insulin resistance, which can lead to the onset of diabetes and obesity. A prior study of a soil-derived organometallic complex (OMC) showed that supplementation reduces glucose and body mass in diabetic mice. The goal of this study was to test the efficacy of a similar OMC compound on the mitigation of hepatic steatosis induced from a HFD. Six-week-old male Sprague-Dawley rats (n=42) were divided into the following diet groups: standard rodent chow or 60% kcal from fat high fat diet (mainly lard) for 10-weeks. Rats were further divided into OMC treatment groups with OMC added to their drinking water: 0 mg/ml, 0.6 mg/ml or 3.0mg/ml OMC. At 10 weeks, study animals were euthanized with sodium pentobarbital (200 mg/kg, i.p.) and cardiac plasma as well as liver samples were collected and stored at -80° C until further analyses. Plasma ALT and AST as well as liver triglyceride and free glycerol concentrations were measured using commercially available kits. To assess cellular injury, aspartate transaminase (AST; released mainly from injured cardiac and liver cells) and alanine transaminase (ALT; released mainly from injured liver cells) were examined. Rats fed HFD had elevated plasma ALT activity, which was prevented by treatment with the high dose of OMC (p<0.05). No changes in plasma AST activity were detected. Examination of liver triglyceride and free glycerol concentrations showed increased fat accumulation in the liver of rats consuming HFD (Two-Way ANOVA, p<0.001). OMC did not prevent this increase. These findings suggest that, although OMC does not prevent the accumulation of lipids in the liver of rats fed HFD, it does mitigate liver injury resulting from excess dietary intake of saturated fats.

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2019-05

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The Effects of Time Restricted Feeding on Mood

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Intermittent Fasting (IF) is defined as a cyclical eating pattern where an individual will fast for a specific increment of time, followed by caloric intake periods. Fasting is a crucial part of our ancestors’ adaptation to the stresses of famine

Intermittent Fasting (IF) is defined as a cyclical eating pattern where an individual will fast for a specific increment of time, followed by caloric intake periods. Fasting is a crucial part of our ancestors’ adaptation to the stresses of famine in order to maintain mental acuity and physical abilities during food deprivation. IF influences physiological changes such as: triggers protective metabolic pathways, increases metabolic flexibility and resilience, promotes DNA repair and autophagy, increases microbiome diversity and restores the natural cyclical fluctuations of the gut, increases BDNF expression in mood regulating neuronal circuits, and enhances synaptic plasticity of the brain. Research on the underlying causes of mood disorders has linked impairments in neuroplasticity and cellular resilience to this pathophysiology, which fasting could mitigate. Depression and anxiety are reported as the top impediments to academic performance. Thus, an easily implemented treatment such as intermittent fasting may be an option for combating impaired mental health in college students. This research study tested time restricted feeding (TRF) and its impact on mood states. It was hypothesized that: if college students follow a time restricted feeding pattern, then they will be less moody due to TRF’s effects on the metabolism, brain, and gut. The study consisted of 11 college students: 5 following a four-week adherence to TRF (8am-4pm eating window) and 6 in the control group. The POMS questionnaire was used to measure mood states. The participants height, weight, BMI, body fat %, and POMS scores were tested at the beginning and end of the 4 week intervention. The results were as follows: weight p=0.112 (statistical trend), BMI p=0.058 (nearly significant), body fat % p=0.114 (statistical trend), POMS p=0.014 (statistically significant). The data suggests that following a TRF eating pattern can decrease moodiness and improve mood states.

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2019-05

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Examination of an Organometallic Complex on Insulin Resistance in Periadolescent Male Rats Following a 10-week High Fat Diet

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With the rising prevalence of obesity and diabetes, novel treatments to help mitigate or prevent symptoms of these conditions are warranted. Prior studies have shown that fossilized plant materials found in soil lowers blood sugar in a mouse model of

With the rising prevalence of obesity and diabetes, novel treatments to help mitigate or prevent symptoms of these conditions are warranted. Prior studies have shown that fossilized plant materials found in soil lowers blood sugar in a mouse model of diabetes. The goal of this study is to determine whether a similar organometallic complex (OMC) could prevent insulin resistance in the skeletal muscle brought on by chronic high fat intake by examining the protein expression of key enzymes in the insulin signaling pathway and examining glucoregulatory measures. Six-week-old periadolescent male Sprague-Dawley rats (n=42) were randomly chosen to be fed either a high fat diet (HFD) (20% protein, 20% carbohydrates [6.8% sucrose], 60% fat) or a standard chow diet (18.9% protein, 57.33% carbohydrates, 5% fat) for 10 weeks. Rats from each diet group were then randomly assigned to one of three doses of OMC (0, 0.6, 3.0 mg/mL), which was added to their drinking water and fasting blood glucose was measured at baseline and again at 10 weeks. After 10 weeks, rats were euthanized, and soleus muscle samples were isolated, snap-frozen, and stored at -80°C until analyses. Fasting plasma glucose was measured using a commercially available glucose oxidase kit. Following 6 and 10 weeks, HFD rats developed significant hyperglycemia (p<0.001 and p=0.025) compared to chow controls which was prevented by high dose OMC (p=0.021). After 10 weeks, there were significant differences in fasting serum insulin between diets (p=0.009) where levels were higher in HFD rats. No significant difference was seen in p-PI3K expression between groups. These results suggest that OMC could prevent insulin resistance by reducing hyperglycemia. Further studies are needed to characterize the effects of diet and OMC on the insulin signaling pathway in skeletal muscle, the main site of postprandial glucose disposal. This study was supported by a grant from Isagenix International LLC as well as funds from Barrett, the Honors College at Arizona State University, Tempe Campus.

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2018-12

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An Urban Diet Impairs Tibial Vasodilation in Mourning Doves (Zenaida macroura)

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Birds maintain resting plasma glucose concentrations (pGlu) nearly twice that of comparably sized mammals. Despite this, birds do not incur much of the oxidative tissue damage that might be expected from a high pGlu. Their ability to stave off oxidative

Birds maintain resting plasma glucose concentrations (pGlu) nearly twice that of comparably sized mammals. Despite this, birds do not incur much of the oxidative tissue damage that might be expected from a high pGlu. Their ability to stave off oxidative damage allows birds to serve as a negative model of hyperglycemia-related complications, making them ideal for the development of new diabetes treatments with the potential for human application. Previous studies conducted by the Sweazea Lab at Arizona State University aimed to use diet as a means to raise blood glucose in mourning doves (Zenaida macroura) in order to better understand the mechanisms they utilize to stave off oxidative damage. These protocols used dietary interventions—a 60% high fat (HF) “chow” diet, and a high carbohydrate (HC) white bread diet—but were unsuccessful in inducing pathologies. Based on this research, we hypothesized that a model of an urban diet (high in fat, refined carbohydrates, and sodium) might impair vasodilation, as the effect of this diet on birds is currently unknown. We found that tibial vasodilation was significantly impaired in birds fed an urban diet compared to those fed a seed diet. Unexpectedly, vasodilation in the urban diet group was comparable to data of wild-caught birds from previous research, possibly indicating that the birds had already been eating a diet similar to this study’s urban diet before they were caught. This may constitute evidence that the seed diet improved vasodilation while the urban diet more closely mimicked the diet of the birds before the trial, suggesting that the model of the urban diet acted as the control diet in this context. This study is the first step in elucidating avian mechanisms for dealing with diabetogenic diets and has potential to aid in the development of treatments for humans with metabolic syndrome.

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2020-05

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Testing the Anti-Glycemic Effect of Commercial Apple Cider Vinegar Pills

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A recent meta-analysis concluded that vinegar consumption could be considered effective adjunct therapy for improving glycemic control. Glycemic control strategies are useful for diabetic and pre-diabetic patients as a way of managing the symptoms of disease. However, liquid vinegar consumption

A recent meta-analysis concluded that vinegar consumption could be considered effective adjunct therapy for improving glycemic control. Glycemic control strategies are useful for diabetic and pre-diabetic patients as a way of managing the symptoms of disease. However, liquid vinegar consumption is often poorly tolerated and ingestion can invoke nausea. This pilot study examined the effect of liquid vinegar versus commercial vinegar pills on postprandial glycemia in 12 healthy adults. All participants were healthy with fasting blood glucose averaging 91mg/dl. This study examined the efficacy of liquid vinegar ingestion (25 g apple cider vinegar [1.25 g acetic acid]) versus vinegar pill ingestion (4 vinegar tablets [1.5 g acetic acid] either consumed whole or crushed and then dissolved in water) on postprandial glycemia. At 30 minutes following a standard test meal (bagel + jelly + juice; 106 g carbohydrate), blood glucose concentrations were reduced 12% in comparison to the pill groups or to a no vinegar control (135.6±15.8, 154.3±22.2, 152.7±30.6, and 157.7±22.8 mg/dl for the liquid vinegar, whole pill, crushed pill, and control groups respectively; p=0.023). These data suggest that in healthy adults, four commercial vinegar pills with a reported acetic acid content of 1.5 g acetic acid are not effective for improving glycemic control.

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2018-05

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AMBROFIT: A Research-Driven Practicum in Nutritional Product Development

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Abstract Ambrofit is a company I founded in February 2014 whose overarching goal is to bridge the gap between science and supplements. This thesis project is as an extension of, and upgrade to, Ambrofit's work. The project begins with a

Abstract Ambrofit is a company I founded in February 2014 whose overarching goal is to bridge the gap between science and supplements. This thesis project is as an extension of, and upgrade to, Ambrofit's work. The project begins with a brief discussion of the supplement industry, motivating the problem which myself and Ambrofit are trying to solve. It addresses the shortcomings of the industry, its regulatory history, and the causal factors which create the industry's environment. As the main part of the project, I design and execute a systematic, evidence-based nutritional product formulation process to create an scientifically sound ergogenic aid which can reliably accelerate training adaptations. The methodology starts with a round of exploratory research to discover potential ingredients then systematically analyzes each ingredient in multiple rounds of effectiveness and safety screenings until the final formula can be synthesized. Ergogenics were the focus of this project because Ambrofit's current product is an ergogenic aid, but I will apply this same process to formulate Ambrofit's whole product line in the future. The second arm of the project is a clinical study protocol design - an evidence-based product created from secondary research is a good start, but ultimately, the formula must be validated by direct research. The protocol describes an 8-week study with well-trained subjects which would either support or reject the formula's ability to accelerate anaerobic training adaptations. The project concludes with a discussion and application of Ambrofit's marketing. This part of the project was done with boots-on-the-ground; Ambrofit is already operating commercially, so I was able test marketing ideas live and evaluate their performance.

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2018-05

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RAGE Deletion Reduces Myocardial Injury in High-Fat Diet-Fed Mice

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The development of the Diabetic Physiological state is influenced by the Receptor for Advanced Glycation End Products (RAGE). This receptor was discovered in 1992, and the accumulation of research on this subject has been extensive. Structural characterization studies of the

The development of the Diabetic Physiological state is influenced by the Receptor for Advanced Glycation End Products (RAGE). This receptor was discovered in 1992, and the accumulation of research on this subject has been extensive. Structural characterization studies of the RAGE protein have shown that it is a transmembrane protein that binds a number of different motile ligands. The diversity of ligands that can attach to the binding domain is the primary factor that allows for RAGE to exhibit its wide-range effects on host cells. Two different studies were completed: one study dealt with the role of IAPP in beta cell death, and the second study was related to RAGE influence on cardiomyocytes and, more specifically, it was related to cardiac cell death. After the completion of the two studies, a comprehensive report was written for each topic. The two papers were merged into a single document. Molecular studies are important for understanding the underlying mechanisms that motivate pathophysiological presentation. In addition to a molecular understanding of the development of diabetes, a clinical research study was completed through the examination of appropriate literature sources. This clinical aspect allowed for the progression of different phases in the research process. A relationship between vinegar and lower plasma glucose was found. The exact mechanism behind this relationship will be studied in the future.

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2015-05

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A 15-Minute Walk: The Short Term Effect of Low Intensity Physical Activity on the Hunger Levels of Pre-diabetic, Obese Adults

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Physical activity as a health or nutrition related intervention might stimulate appetite and increase hunger due to increased energy expenditure. This study analyzed the effect of a postprandial 15-minute walk on the hunger and energy intake of 10 obese, pre-diabetic

Physical activity as a health or nutrition related intervention might stimulate appetite and increase hunger due to increased energy expenditure. This study analyzed the effect of a postprandial 15-minute walk on the hunger and energy intake of 10 obese, pre-diabetic adults. Subjects participated in three 4-hour trials: a walk treatment (consume highly glycemic meal, walk for 15 minutes at a moderate pace, and rest for 4 hours), a fiber treatment (consume highly glycemic meal enriched with soluble fiber and rest for 4 hours), and a control treatment (consume highly glycemic meal without fiber and rest for 4 hours). The effects of each treatment on hunger and energy intake were measured using a Likert scale analysis (ranging from "completely satisfied" to "extremely hungry") at 4 hours post-treatment and pre/ post 24-hour dietary logs. The results showed no significant increase or decrease on hunger or energy intake for both the walk and the fiber treatment compared to the control treatment. This denies the idea that physical activity might increase short-term hunger, and supports the use of physical activity as a viable nutrition related intervention tool.

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2015-05

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Examining the Effect of Vinegar on Glucose Response

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The objective of this randomized, single-blind crossover study was to examine the effect of vinegar on the blood glucose response to meal ingestion. This study was associated with a companion study Is Apple Cider Vinegar Effective for Reducing Heartburn

The objective of this randomized, single-blind crossover study was to examine the effect of vinegar on the blood glucose response to meal ingestion. This study was associated with a companion study Is Apple Cider Vinegar Effective for Reducing Heartburn Symptoms Related to Gastroesophageal Reflux Disease. Glucose meters were utilized to measure blood glucose levels immediately prior to, and at four ½ hour intervals following meal ingestion. Previous studies have demonstrated that vinegar modulates the meal-time glucose response. Hence an alternative hypothesis was used: that a significant difference will be observed between the control and the vinegar groups. The results from the study were not significant likely due to a small sample size. The test meal eaten with a drink composed of vinegar diluted in water appeared to be most effective at decreasing the overall change in postprandial blood glucose. The vinegar drink also played a role in decreasing the peak glucose level at 30 minutes post-meal.

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2015-05

Supplementation of Vitamin B6 and Tryptophan: The Effects on Mood States Among College Club Sport Athletes

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There are many studies on vitamin B6 (pyrodoxine) or tryptophan (Trp) as a way to increase mood but there are little to no studies with these two nutrients supplemented together. Trp is the precursor to serotonin that requires the cofactor

There are many studies on vitamin B6 (pyrodoxine) or tryptophan (Trp) as a way to increase mood but there are little to no studies with these two nutrients supplemented together. Trp is the precursor to serotonin that requires the cofactor pyridoxal phosphate (PLP). Serotonin plays a role in mood, sleep, appetite, and other wellbeing aspects and it is believed that low levels of serotonin is associated with the risk of developing depression, anxiety, and bipolar disorders. The amount of free Trp that can pass the blood-brain barrier (BBB) is influenced by factors such as cortisol, insulin, and competition from branch chain amino acids (BCAA). College students who exercise on a regular basis and participate in club sports may experience higher cortisol levels from stress of college and higher physical activity. Cortisol decreases the Trp levels in the plasma while BCAAs compete with Trp to pass through the BBB. Insulin promotes the passage of free Trp through the BBB. In the present study, 28 healthy active college students (21.0 ± 2.1 years, 24.5± 3.1 kg/m2) were divided into three groups: vitamin B6 (n=11), Trp (n=10), or both (n=10) (2 did not complete study). Blood serum pyridoxine levels and mood states were measured at baseline and at 4 weeks with Profile of Mood States (POMS), Depression Anxiety Stress Survey (DASS), Life Orientation Test-Revised (LOT-R), and Epworth sleep scale. In the combined sample, the total POMS score improved during the study (p=0.039) and the total DASS score tended to improve during the study (p=0.068). Thus, mean depression scores for all participants decreased during the 4-week supplementation study. However, there were no time x treatment effects noted at study completion. At baseline 18% of the participants were marginally deficient in vitamin B6 (serum pyridoxine <30nmol/L), and their total POMS score was raised 78% in comparison to participants with adequate vitamin B6 status (p=0.08). DASS scores were raised 48% in vitamin B6 deficient participants versus those with adequate vitamin B6 status (p=0.243). There were no significant changes (time or time x treatment) during the course of the study for the LOT-R or sleep scores. In summary, vitamin B6 deficiency in college student athletes was remarkably high (18%) compared to the national average reported by the CDC in 2012 (10.5%), and participants with vitamin B6 deficiency displayed heightened unfavorable mood states. Moreover, supplementation with vitamin B6, tryptophan, or vitamin B6 and tryptophan improved mood state in college student athletes, but there were no differences between treatments.

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2016-05