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Skeletal muscle (SM) mitochondria generate the majority of adenosine triphosphate (ATP) in SM, and help regulate whole-body energy expenditure. Obesity is associated with alterations in SM mitochondria, which are unique with respect to their arrangement within cells; some mitochondria are located directly beneath the sarcolemma (i.e., subsarcolemmal (SS) mitochondria), while

Skeletal muscle (SM) mitochondria generate the majority of adenosine triphosphate (ATP) in SM, and help regulate whole-body energy expenditure. Obesity is associated with alterations in SM mitochondria, which are unique with respect to their arrangement within cells; some mitochondria are located directly beneath the sarcolemma (i.e., subsarcolemmal (SS) mitochondria), while other are nested between the myofibrils (i.e., intermyofibrillar (IMF) mitochondria). Functional and proteome differences specific to SS versus IMF mitochondria in obese individuals may contribute to reduced capacity for muscle ATP production seen in obesity. The overall goals of this work were to (1) isolate functional muscle SS and IMF mitochondria from lean and obese individuals, (2) assess enzyme activities associated with the electron transport chain and ATP production, (3) determine if elevated plasma amino acids enhance SS and IMF mitochondrial respiration and ATP production rates in SM of obese humans, and (4) determine differences in mitochondrial proteome regulating energy metabolism and key biological processes associated with SS and IMF mitochondria between lean and obese humans.

Polarography was used to determine functional differences in isolated SS and IMF mitochondria between lean (37 ± 3 yrs; n = 10) and obese (35 ± 3 yrs; n = 11) subjects during either saline (control) or amino acid (AA) infusions. AA infusion increased ADP-stimulated respiration (i.e., coupled respiration), non-ADP stimulated respiration (i.e., uncoupled respiration), and ATP production rates in SS, but not IMF mitochondria in lean (n = 10; P < 0.05). Neither infusion increased any of the above parameters in muscle SS or IMF mitochondria of the obese subjects.

Using label free quantitative mass spectrometry, we determined differences in proteomes of SM SS and IMF mitochondria between lean (33 ± 3 yrs; n = 16) and obese (32 ± 3 yrs; n = 17) subjects. Differentially-expressed mitochondrial proteins in SS versus IMF mitochondria of obese subjects were associated with biological processes that regulate: electron transport chain (P<0.0001), citric acid cycle (P<0.0001), oxidative phosphorylation (P<0.001), branched-chain amino acid degradation, (P<0.0001), and fatty acid degradation (P<0.001). Overall, these findings show that obesity is associated with redistribution of key biological processes within the mitochondrial reticulum responsible for regulating energy metabolism in human skeletal muscle.
ContributorsKras, Katon Anthony (Author) / Katsanos, Christos (Thesis advisor) / Chandler, Douglas (Committee member) / Dinu, Valentin (Committee member) / Mor, Tsafrir S. (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Background: The prevalence of childhood obesity has disproportionately affected Latino youth and can be seen with an increase incidence of Type 2 Diabetes. This increase in obesity can be attributed to physical inactivity. Increases in social support and self-efficacy are independently related to increases in physical activity. A lifestyle intervention

Background: The prevalence of childhood obesity has disproportionately affected Latino youth and can be seen with an increase incidence of Type 2 Diabetes. This increase in obesity can be attributed to physical inactivity. Increases in social support and self-efficacy are independently related to increases in physical activity. A lifestyle intervention can lead to increases in social support, self-efficacy and physical activity. Objective/Hypothesis: The objective of this study was to determine whether a 12-week lifestyle intervention could increase social support, self-efficacy and physical activity in obese Latino adolescents that participated in the intervention. It was hypothesized that adolescents that participated in the intervention would increase self-efficacy, social support from family and friends, and physical activity compared to their control counterparts. Study Design/Participants: In a randomized control trial, there were 125 Latino (n= 60 experimental group; n= 65 control group; mean age = 15.17 +- 1.65 Males n = 60; n = 65 females) participants included in this study. Participants were also required to have a BMI percentile >= 95th percentile for age and gender or BMI >= 30 kg/m2. Methods: The intervention, which was developed using the Social Cognitive Theory had components focusing on social support and self-efficacy and also consisted of nutrition education classes and physical activity sessions for 12 weeks. The psychosocial constructs of self-efficacy and social support were measured using the Adolescent Self-Efficacy for Diet and Activity Behaviors and Adolescent Social Support for Diet and Exercise Survey, respectively. Physical activity was assessed by the 3-day Physical Activity Recall. Results: We found significant increases in social support in family (p = 0.042) and vigorous physical activity (p = 0.001). There was also a significant difference between control and treatment group for moderate to vigorous physical activity after the intervention (p = 0.027). There were no changes in social support from friends or self-efficacy. Conclusion: We concluded that a 12-week lifestyle intervention did lead to changes in social support and physical activity behaviors. These changes could have been influenced by the intervention as they were measured these constructs pre/post intervention.
ContributorsRahman, Hanna (Author) / Shaibi, Gabriel (Thesis director) / Hoffner, Kristin (Committee member) / School of Nutrition and Health Promotion (Contributor) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
DNA methylation, a subset of epigenetics, has been found to be a significant marker associated with variations in gene expression and activity across the entire human genome. As of now, however, there is little to no information about how DNA methylation varies between different tissues inside a singular person's body.

DNA methylation, a subset of epigenetics, has been found to be a significant marker associated with variations in gene expression and activity across the entire human genome. As of now, however, there is little to no information about how DNA methylation varies between different tissues inside a singular person's body. By using research data from a preliminary study of lean and obese clinical subjects, this study attempts to put together a profile of the differences in DNA methylation that can be observed between two particular body tissues from this subject group: blood and skeletal muscle. This study allows us to start describing the changes that occur at the epigenetic level that influence how differently these two tissues operate, along with seeing how these tissues change between individuals of different weight classes, especially in the context of the development of symptoms of Type 2 Diabetes.
ContributorsRappazzo, Micah Gabriel (Author) / Coletta, Dawn (Thesis director) / Katsanos, Christos (Committee member) / Dinu, Valentin (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / Department of Psychology (Contributor)
Created2013-12
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Description
Problem: Overweight and obesity are global issues. There are several strategies for weight loss and maintenance as well as general lifestyle change for overall better health. The goal is to find an easy and convenient way for people to track their food intake, either for personal use and improvement, or

Problem: Overweight and obesity are global issues. There are several strategies for weight loss and maintenance as well as general lifestyle change for overall better health. The goal is to find an easy and convenient way for people to track their food intake, either for personal use and improvement, or to be used by professionals such as registered dietitians to gather data and help improve diet. Currently food journals, food frequency questionnaires and 24-hour recall are methods that are used by registered dietitians to get an idea of what is general diet is like from their patients or clients. It was proposed that pictures taken of the meal with a phone could be used as a method of recording food intake. It would be quick and extremely easy on the client; then everything from portion size, to type of food and toppings could be analyzed quickly and conveniently. If effective it could also give rise to the ability for foods to be analyzed immediately with the text or email of the picture. Methods: subjects already participating in a separate study where they were instructed to take pictures of their meals for a difference purpose were recruited. There recorded diet intake with phone pictures were able to be used from seven subjects. Subjects took a snapshot of their meals for 3 separate days and also logged on and completed a 24 hour recall with the ASA website. The pictures were analyzed and food intake, based off the pictures was entered in the program Food Processor to generate a nutritional report. The results from the ASA 24 hour recall, based on what the subject entered, were compared to the nutritional report, generated based on review of the pictures. Nutrient values that were compared include: total energy intake (calories), protein, carbohydrates, fat, vitamin C, calcium and fiber. This was done to test if the pictures could be used as a valid source. Results: It was found that there were several problems with using the pictures as a method of analyzing food intake. Out of the seven subjects the result of only one subject was close between the two methods. All other results of calculated nutrient intake varied significantly and it did not prove to be effective to use pictures to analyze food intake. Conclusions: food intake recorded by picture method may prove to be useful in the future, however there would need to be greater compliance and training on picturing food that can be accurately analyzed. Short written explanation of food type and cooking method etc. would be most beneficial to include with actual picture. Pictures of food intake may be useful in other professional areas but as of now are not useful to generate nutritional reports.
ContributorsLouden, Karina Arianne (Author) / Johnston, Carol (Thesis director) / Morse, Lisa (Committee member) / Appel, Christy (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2013-05
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Description
Many individuals are not following healthy lifestyles as evidenced by the high obesity rates and poor physical activity levels. Many do not know how to eat healthy and exercise effectively, especially given busy schedules and no time to cook or go to the gym. However, people do spend a significant

Many individuals are not following healthy lifestyles as evidenced by the high obesity rates and poor physical activity levels. Many do not know how to eat healthy and exercise effectively, especially given busy schedules and no time to cook or go to the gym. However, people do spend a significant amount of time on their mobile device using social media. This outlet can potentially be used to inspire and teach individuals how to cook healthy simple meals, or find motivation to get off the couch for some exercise. In this study, strategies were identified that would increase the comments, likes, and followers of the investigator's Instagrams, which were designed to motivate followers to live a healthier lifestyle. Initially, 462 posts were assessed retrospectively to determine how the number of likes and comments were influenced by hashtags, category of posts (nutrition, fitness, or inspiration), and/or type of app, PicPlayPost, Instaframe, and the updated Instagram. These results were used in a 1-month prospective study to increase likes and followers to the investigator's Instagrams. In the retrospective study, it was determined that hashtags influenced the number of comments and likes across the categories and that the PicPlayPost app increased the likes in all categories. Hence, for the prospective study, the investigator wrote 1 nutrition and 1 fitness post daily for 28 days using a minimum of 15 hashtags per post. In addition, 3 nutrition posts and 3 fitness posts per week used the PicPlayPost app. This posting strategy increased the number of likes per post by 100%, and the number of followers increased from 369 to 1082 in one month. Interestingly, the nutrition posts received 27% more likes than the fitness posts, and the PicPlayPost app increased comments by 134%. In conclusion, the use of hashtags, PicPlayPost, and Instaframe apps increased the likes and comments on social media. These strategies may increase audience's attention on a certain topic and be used to improve individuals' lifestyles.
ContributorsTomasso, Bernice Grace (Author) / Johnston, Carol (Thesis director) / Dixon, Kathy (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2014-05
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Description
In the United States, the prevalence of pediatric obesity has increased to 17% in the general population and even more so in the Hispanic pediatric population to 22.4%. These children are at a higher risk for associated comorbidities, including cardiovascular disease and insulin resistance. The purpose of the following study

In the United States, the prevalence of pediatric obesity has increased to 17% in the general population and even more so in the Hispanic pediatric population to 22.4%. These children are at a higher risk for associated comorbidities, including cardiovascular disease and insulin resistance. The purpose of the following study is to determine the effectiveness of the Nutrition and Health Awareness curriculum at reducing childhood obesity by evaluating alterations in the gut microbial composition, diet, and overall health of the students throughout the five-week program. Nutrition and Health Awareness (NHA) is a student organization that strives to reduce the prevalence of obesity, diabetes, and cardiovascular diseases, specifically in children, by providing active nutrition education services through peer mentoring in elementary schools and community programs. This study went through ASU's Institutional Review Board process and all forms were translated into Spanish. The control group maintained their normal routines and the experimental group received the 5 week NHA program and then continued with their normal routines. Anthropometric measures (Body Mass Index, waist-to-hip ratio, and blood pressure), diet measures (Hispanic food frequency questionnaire), fecal swabs, and content surveys were collected on weeks 0, 5, and 8. Contrary to expected, alpha diversity, kilocalorie intake, and macronutrient intake decreased as the study progressed for both the control and experimental groups. Anthropometric measurements were relatively stable. Though not statistically significant, the greatest difference in time points is between weeks 1 and 8. This decrease in alpha diversity and kilocalorie intake could be due to a change in environment since the children started school on week 8. Future implications of this study are that parental involvement is necessary for an effective, sustainable change in these children. More research in different settings is necessary to determine NHA's effectiveness
ContributorsPatel, Kapila Cristina (Author) / Krajmalnik-Brown, Rosa (Thesis director) / Whisner, Corrie (Committee member) / School of Nutrition and Health Promotion (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Obesity is a rising problem in the country today, and countless efforts have been made to achieve long-term weight loss. Recent research indicates that through the manipulation of Brown Adipose Tissue (BAT) activity within the body, weight loss can be achieved. The goal of this experiment was to understand the

Obesity is a rising problem in the country today, and countless efforts have been made to achieve long-term weight loss. Recent research indicates that through the manipulation of Brown Adipose Tissue (BAT) activity within the body, weight loss can be achieved. The goal of this experiment was to understand the effects of a high-fat diet (HFD) on BAT activity and diet-induced thermogenesis in cold-stressed rats. It was predicted that the HFD would stimulate BAT activity and this would then drive up thermogenic activity to promote weight loss. Diet-induced thermogenesis was predicted to increase during the HFD phase of this experiment as the body would require more energy to digest the more calorically dense food. Upon arrival at six weeks of age, the rats were started on a low-fat diet (LFD) ad libitum for three weeks. They were then transitioned into a HFD ad libitum for the next 8 weeks. Throughout the experiment, the rats were maintained in a cold-stressed environment at 22°C. It was determined that one of the rats was identified as obesity prone, while the other three rats were obesity resistant based on the rate of weight gain and caloric intake. Obesity can decrease metabolism in the body for many reasons, yet it was not seen in this experiment that the obesity prone rat demonstrated decreased metabolism in comparison to the others. Based on the differences seen in the reference temperatures and the BAT temperatures, it was determined that the BAT was active throughout both the LFD and HFD phases. However, the BAT did not rise significantly during the HFD period as expected. More research is indicated with a larger sample size to determine if BAT activity does continue to increase during a HFD as a result of diet-induced thermogenesis.
ContributorsLubold, Jessica Marie Sarah (Author) / Morse, Lisa (Thesis director) / Herman, Richard (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Obesity and its underlying insulin resistance are caused by environmental and genetic factors. DNA methylation provides a mechanism by which environmental factors can regulate transcriptional activity. The overall goal of the work herein was to (1) identify alterations in DNA methylation in human skeletal muscle with obesity and its underlying

Obesity and its underlying insulin resistance are caused by environmental and genetic factors. DNA methylation provides a mechanism by which environmental factors can regulate transcriptional activity. The overall goal of the work herein was to (1) identify alterations in DNA methylation in human skeletal muscle with obesity and its underlying insulin resistance, (2) to determine if these changes in methylation can be altered through weight-loss induced by bariatric surgery, and (3) to identify DNA methylation biomarkers in whole blood that can be used as a surrogate for skeletal muscle.

Assessment of DNA methylation was performed on human skeletal muscle and blood using reduced representation bisulfite sequencing (RRBS) for high-throughput identification and pyrosequencing for site-specific confirmation. Sorbin and SH3 homology domain 3 (SORBS3) was identified in skeletal muscle to be increased in methylation (+5.0 to +24.4 %) in the promoter and 5’untranslated region (UTR) in the obese participants (n= 10) compared to lean (n=12), and this finding corresponded with a decrease in gene expression (fold change: -1.9, P=0.0001). Furthermore, SORBS3 was demonstrated in a separate cohort of morbidly obese participants (n=7) undergoing weight-loss induced by surgery, to decrease in methylation (-5.6 to -24.2%) and increase in gene expression (fold change: +1.7; P=0.05) post-surgery. Moreover, SORBS3 promoter methylation was demonstrated in vitro to inhibit transcriptional activity (P=0.000003). The methylation and transcriptional changes for SORBS3 were significantly (P≤0.05) correlated with obesity measures and fasting insulin levels. SORBS3 was not identified in the blood methylation analysis of lean (n=10) and obese (n=10) participants suggesting that it is a muscle specific marker. However, solute carrier family 19 member 1 (SLC19A1) was identified in blood and skeletal muscle to have decreased 5’UTR methylation in obese participants, and this was significantly (P≤0.05) predicted by insulin sensitivity.

These findings suggest SLC19A1 as a potential blood-based biomarker for obese, insulin resistant states. The collective findings of SORBS3 DNA methylation and gene expression present an exciting novel target in skeletal muscle for further understanding obesity and its underlying insulin resistance. Moreover, the dynamic changes to SORBS3 in response to metabolic improvements and weight-loss induced by surgery.
ContributorsDay, Samantha Elaine (Author) / Coletta, Dawn K. (Thesis advisor) / Katsanos, Christos (Committee member) / Mandarino, Lawrence J. (Committee member) / Shaibi, Gabriel Q. (Committee member) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2017
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Description
This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems

This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems biology level, I provide new targets to explore for the research community. Furthermore I present a new online web resource that unifies various bioinformatics databases to enable discovery of relevant features in 3D protein structures.
ContributorsMielke, Clinton (Author) / Mandarino, Lawrence (Committee member) / LaBaer, Joshua (Committee member) / Magee, D. Mitchell (Committee member) / Dinu, Valentin (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013
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Description
The aim of this study is to understand the relationship among physical fitness, leisure-time activity levels, measures of body composition, and assessments of emotion toward physical activity in individuals with Down syndrome (DS). This is important because it could help individuals understand the importance of physical activity in this population.

The aim of this study is to understand the relationship among physical fitness, leisure-time activity levels, measures of body composition, and assessments of emotion toward physical activity in individuals with Down syndrome (DS). This is important because it could help individuals understand the importance of physical activity in this population. The BMI, waist circumference, height, weight, body fat percentage, and non-exercise estimation of aerobic capacity along with the temporary state of emotion toward physical activity of thirty participants with DS were measured. The results of our study show that individuals with DS who are more physically fit have less body fat and a lower BMI. They also took part in more leisure-time activity and expressed more effort during physical activity.
ContributorsSnow, Michelle Jeannette (Author) / Ringenbach, Shannon (Thesis director) / Chen, Chih-Chia (Committee member) / Maraj, Brian (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2013-05