Matching Items (7)

137205-Thumbnail Image.png

Hyperinsulinemia

Description

Concurrent with the epidemic of childhood obesity (17% of adolescents), an unprecedented world-wide increase in the prevalence of several adiposity-related complications (including fatty liver disease (hepatic steatosis), type 2 diabetes

Concurrent with the epidemic of childhood obesity (17% of adolescents), an unprecedented world-wide increase in the prevalence of several adiposity-related complications (including fatty liver disease (hepatic steatosis), type 2 diabetes and early cardiovascular disorders) in this age group, has emerged. Two principle environmental variables play an essential role in the development and maintenance of obesity and in disturbing glucose homeostasis: a lack of physical exercise and overnutrition, i.e., high carbohydrate and high fat diets (HFD). It was our laboratory's intention to develop a rodent model to examine whether the metabolic instability observed in human pubertal children is also present in maturing rats and whether a HFD during this maturational period enhances adipose-related complications with or without an increase in body weight. We hypothesized that maturing Sprague-Dawley rats would reveal a profile of metabolic disturbances and that a disruption of the hyperbolic arrangement between insulin sensitivity and insulin release would be evident (statistically significant changes in fasting hyperinsulinemia, insulin resistance, and insulin release) indicating a high risk environment for future cardiometabolic diseases. It was observed that pubertal rats are metabolically impaired and that a HFD substantially enhances metabolic deficits with marked disturbance in insulin sensitivity (hyperinsulinemia). Additionally, substantial lipogenesis was observed in visceral and liver tissue, potentially as a result of hyperinsulinemia. Both phenotypes of maturing rats exposed to a HFD (obesity prone and obesity resistant) demonstrated "metabolic obesity" regardless of physical phenotype. These outcomes have relevance in the context of public health, particularly if lipocentricity is viewed as an essential element in the challenge of preventing and/or treating perturbations to the metabolic health of pubertal children.

Contributors

Agent

Created

Date Created
  • 2014-05

132581-Thumbnail Image.png

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

Description

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.

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.

Contributors

Agent

Created

Date Created
  • 2019-05

158091-Thumbnail Image.png

Evaluation of an Organic Mineral Complex on the Development of Cardiovascular Disease Risk Following a 10-week High-Fat Diet

Description

According to the World Health Organization, obesity has nearly tripled since 1975 and forty-one million children under the age of 5 are overweight or obese (World Health Organization, 2018). Exercise

According to the World Health Organization, obesity has nearly tripled since 1975 and forty-one million children under the age of 5 are overweight or obese (World Health Organization, 2018). Exercise is a potential intervention to prevent obesity-induced cardiovascular complications as exercise training has been shown to aid nitric oxide (NO) production as well as preserving endothelial function in obese mice (Silva et al., 2016). A soil-derived organic mineral compound (OMC) has been shown to lower blood sugar in diabetic mice (Deneau et al., 2011). Prior research has shown that, while OMC did not prevent high fat diet (HFD)-induced increases in body fat in male Sprague-Dawley rats, it was effective at preventing HFD-induced impaired vasodilation (M. S. Crawford et al., 2019). Six-weeks of HFD has been shown to impair vasodilation through oxidative-stress mediated scavenging of NO as well as upregulation of inflammatory pathways including inducible nitric oxide synthase (iNOS) and cyclooxygenase (Karen L. Sweazea et al., 2010). Therefore, the aim of the present study was to determine whether OMC alters protein expression of iNOS and endothelial NOS (eNOS) in the vasculature of rats fed a control or HFD with and without OMC supplementation. Six-week old male Sprague-Dawley rats were fed either a standard chow diet (CHOW) or a HFD composed of 60% kcal from fat for 10 weeks. The rats were administered OMC at doses of 0 mg/mL (control), 0.6 mg/mL, or 3.0 mg/mL added to their drinking water. Following euthanasia with sodium pentobarbital (200 mg/kg, i.p.), mesenteric arteries and the surrounding perivascular adipose tissue were isolated and prepared for Western Blot analyses. Mesenteric arteries from HFD rats had more uncoupled eNOS (p = 0.006) and iNOS protein expression (p = 0.027) than rats fed the control diet. OMC was not effective at preventing the uncoupling of eNOS or increase in iNOS induced by HFD. Perivascular adipose tissue (PVAT) showed no significant difference in iNOS protein expression between diet or OMC treatment groups. These findings suggest that OMC is not likely working through the iNOS or eNOS pathways to improve vasodilation in these rats, but rather, appears to be working through another mechanism.

Contributors

Agent

Created

Date Created
  • 2020

152123-Thumbnail Image.png

Towards a systems biology understanding of metabolic syndrome

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

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.

Contributors

Agent

Created

Date Created
  • 2013

155443-Thumbnail Image.png

Sleep-related mediators of the physical activity and sedentary behavior-cardiometabolic biomarker relationship in middle age adults

Description

Physical activity, sedentary behaviors, and sleep are often associated with cardiometabolic biomarkers commonly found in metabolic syndrome. These relationships are well studied, and yet there are still questions on how

Physical activity, sedentary behaviors, and sleep are often associated with cardiometabolic biomarkers commonly found in metabolic syndrome. These relationships are well studied, and yet there are still questions on how each activity may affect cardiometabolic biomarkers. The objective of this study was to examine data from the BeWell24 studies to evaluate the relationship between objectively measured physical activity and sedentary behaviors and cardiometabolic biomarkers in middle age adults, while also determining if sleep quality and duration mediates this relationship. A group of inactive participants (N = 29, age = 52.1 ± 8.1 years, 38% female) with increased risk for cardiometabolic disease were recruited to participate in BeWell24, a trial testing the impact of a lifestyle-based, multicomponent smartphone application targeting sleep, sedentary, and more active behaviors. During baseline, interim (4 weeks), and posttest visits (8 weeks), biomarker measurements were collected for weight (kg), waist circumference (cm), glucose (mg/dl), insulin (uU/ml), lipids (mg/dl), diastolic and systolic blood pressures (mm Hg), and C reactive protein (mg/L). Participants wore validated wrist and thigh sensors for one week intervals at each time point to measure sedentary behavior, physical activity, and sleep outcomes. Long bouts of sitting time (>30 min) significantly affected triglycerides (beta = .15 (±.07), p<.03); however, no significant mediation effects for sleep quality or duration were present. No other direct effects were observed between physical activity measurements and cardiometabolic biomarkers. The findings of this study suggest that reductions in long bouts of sitting time may support reductions in triglycerides, yet these effects were not mediated by sleep-related improvements.

Contributors

Agent

Created

Date Created
  • 2017

157201-Thumbnail Image.png

Examining the effects of a high fat diet on the development of metabolic syndrome and gut leakiness in male Sprague-Dawley rats

Description

The prevalence of obesity and obesity-related disorders have increased world-wide. In the last decade, the intestinal microbiome has become a major indicator of metabolic and gastrointestinal health. Previous research has

The prevalence of obesity and obesity-related disorders have increased world-wide. In the last decade, the intestinal microbiome has become a major indicator of metabolic and gastrointestinal health. Previous research has shown that high-fat diet (HFD) consumption can alter the microbial composition of the gut by increasing the abundance of gram-positive bacteria associated with the onset of obesity and type 2 diabetes. Although, the most common form of obesity and metabolic syndrome intervention is exercise and diet, these recommendations may not improve severe cases of obesity. Thus, an important relevance of my project was to investigate whether the intake of an organometallic complex (OMC) would prevent the onset of metabolic and gastrointestinal complications associated with high-fat diet intake. I hypothesized that the consumption of a HFD for 6 weeks would promote the development of metabolic and gastrointestinal disease risk factors. Next, it was hypothesized that OMC treatment would decrease metabolic risk factors by improving insulin sensitivity and decreasing weight gain. Finally, I hypothesized that HFD-intake would increase the abundance of gram-positive bacteria associated with gastrointestinal disease. My preliminary data investigated the effects of a 6-week HFD on the development of hepatic steatosis, intestinal permeability and inflammation in male Sprague Dawley rats. I found that a 6-week HFD increases hepatic triglyceride concentrations, plasma endotoxins and promotes the production of pro-inflammatory cytokines in the cecum wall. I then investigated whether OMC treatment could prevent metabolic risk factors in male Sprague-Dawley rats fed a HFD for 10 weeks and found that OMC can mitigate risk factors such hyperglycemia, liver disease, impaired endothelial function, and inflammation. Lastly, I investigated the effects of a 10-week HFD on the gastrointestinal system and found an increase in liver triglycerides and free glycerol and alterations of the distal gut microbiome. My results support the hypothesis that a HFD can promote metabolic risk factors, alter the gut microbiome and increase systemic inflammation and that OMC treatment may help mitigate some of these effects. Together, these studies are among the first to demonstrate the effects of a soil-derived compound on metabolic complications. Additionally, these conclusions also provide an essential basis for future gastrointestinal and microbiome studies of OMC treatment.

Contributors

Agent

Created

Date Created
  • 2019

150129-Thumbnail Image.png

Non-biological factors contribute to increased risk of cardiovascular disease and metabolic syndrome in Mexican-Americans living in metropolitan Phoenix

Description

Among the general US population, cardiovascular disease (CVD) is the main cause of mortality for Mexican-Americans. CVD is less prevalent among Mexican-Americans than non-Hispanic Whites or African Americans. However,

Among the general US population, cardiovascular disease (CVD) is the main cause of mortality for Mexican-Americans. CVD is less prevalent among Mexican-Americans than non-Hispanic Whites or African Americans. However, there is limited research regarding the factors associated with increased CVD risk among Mexican-Americans. Thus, this cross-sectional study was conducted to evaluate the effects of non-biological factors (income, education, employment, acculturation) and diet on CVD risk factors in 75 Mexican-American adults (26 males, 49 females; age=37.6±9.3 y, BMI=28.9±5.3 kg/m2, systolic BP=117±11 mmHg, diastolic BP=73±9 mmHg, LDL cholesterol=114±32 mg/dL, HDL cholesterol=44±11 mg/dL, triglycerides=115±61 mg/dL, serum glucose=92±7 mg/dL). Aside from collecting anthropometric measurements, blood pressure, and measuring fasting blood lipids, glucose, and insulin, information about participants' socioeconomic status, income, employment, education, and acculturation were gathered using a survey. Diet data was collected using the Southwestern Food Frequency Questionnaire. Weight, BMI, and waist circumference were significantly greater for those with a monthly income of <$3000 than for those earning >$3000 (81±15 kg vs. 71±15 kg; 29.8±4.6 kg/m2 vs. 26.5±5.1 kg/m2; 98±12 cm vs. 89±14 cm; respectively) and with an education level of high school graduate or less than for those with some college (84±16 kg vs. 72±14 kg; 30.6±4.2 kg/m2 vs. 26.9±4.9 kg/m2; 100±11 cm vs. 91±13 cm; respectively). HDL-C was higher for those with a monthly income of >$3000 than those earning <$3000 (49±12 mg/dL vs. 41±10 mg/dL), those with some college education than those with high school or less (47±10 mg/dL vs. 37±9 mg/dL), and for those employed than those not employed (46±10 mg/dL vs. 40±12 mg/dL). There was no association between acculturation and CVD risk factors. Percent of energy consumed from fat was greater and percent of energy from carbohydrates was lower in those earning <$3000 monthly than those earning >$3000 (32±5% vs. 29±3%; 52±8% vs. 56±4%; respectively). Greater acculturation to the Anglo culture was negatively correlated with body fat percentage (r=-0.238, p=0.043) and serum glucose (r=-0.265, p=0.024). Overall, these results suggest that factors related to sociocultural and socioeconomic status may affect cardiometabolic disease risk in Mexican-Americans living in the Phoenix metropolitan area.

Contributors

Agent

Created

Date Created
  • 2011