Progress 10/01/05 to 09/30/08
Outputs
OUTPUTS: Studies outlined in this proposal were designed to 1) Determine the effect of a high glycemic index diet on systemic and local oxidative stress. 2) Determine the influence of a high glycemic index diet on whole-body insulin sensitivity, glucose utilization, and insulin signaling. 3) Determine if antioxidant therapy can ameliorate the effects of a high glycemic index diet on oxidative stress and glucose metabolism. Male C57Bl/6 mice were fed a low GI diet (60% amylose/40% amylopectin) or a high GI diet (100% amylopectin) for 16 weeks. To determine the effects of glycemic index on oxidative stress, blood was collected every 4 weeks and plasma levels of oxidative stress markers (TBARS, hydrogen peroxide, TNF-alpha, IL-6) were assayed. After the experimental feeding study, mice were sacrificed and tissues (skeletal muscle, liver, and adipose tissue) were collected and genes involved in oxidative stress were analyzed via real-time PCR analysis. To address the effects of glycemic inex on glucose metabolism, a subset of mice consuming the experimental diets were subjected to glucose tolerance tests. To determine if antioxidant therapy will ameliorate the effects of a high GI diet on oxidative stress and glucose metabolism, mice were fed a high GI diet plus an antioxidant for 16 weeks. The above studies were performed and the results compared to animals fed the high GI diet alone. PARTICIPANTS: Kevin Huggins (PI) - wrote grant, designed experiments, edited manuscript. Suresh Mathews (co-PI) - assisted with oxidative stress measurements. Robert Judd (co-PI) - assisted with study design. Katie Colbert (graduate student) - performed experiments, collected data, wrote manuscript, presented data at national meetings.One master's student (Katie Colbert) was trained under these studies. TARGET AUDIENCES: Primary target audiences were scientists and researchers. Data was primarily disseminated through manuscript and poster presentations at Experimental Biology 2008 and various research forums at Auburn University. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The goal of this study was to determine a mechanism by which dietary carbohydrates with a high glycemic index may lead to detrimental effects such as obesity, insulin resistance, and diabetes. We found that mice consuming the high GI diet had increased adiposity compared to mice fed the low GI diets. These results, taken together, suggest that consumption of a high GI diet causes increased deposition of adipose tissue mass. This result is consistent with the previous literature dealing with the effects of GI on adipose tissue mass. There were no differences in plasma adiponectin, glucose, and insulin levels in these mice. Based on these results, we concluded that there were no overall differences in insulin sensitivity between the two diet groups. Since consumption of high GI diets result in increased postprandial hyperglycemia, we wanted to investigate the effects of GI on oxidative stress in adipose tissue. We have completed our gene expression analysis of the pro-oxidative enzyme, NADPH oxidase, and the anti-oxidant enzymes (superoxide dismustase, catalase, glutathione peroxidase). There were no differences in expression of these genes between the high GI and low GI diet groups. These results indicate that GI does not affect oxidative stress status in the adipose tissue. We conclude that, while high GI diets increased adipose tissue mass, generation of oxidative stress in the adipose tissue is not a mechanism by which high-GI diets elicit this effect. High fat diets have been shown to induce systemic and adipose tissue specific increases in oxidative stress. However, our study is the first to address the type of carbohydrate on oxidative stress. As expected, high fat diet feeding significantly increased the expression of the pro-oxidant enzyme NADPH oxidase and significantly lowered the expression of the anti-oxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase in the adipose tissue. However, there were no significant differences between the high GI and low GI diet groups with high fat feeding. In addition, the high fat diets significantly increased plasma levels of IL-6 and TBARS compared to low fat diets. There were no differences in these plasma metabolites between high GI and low GI animals. These results indicate that while a high fat diet increased the development of insulin resistance and generated increased adipose tissue and systemic oxidative stress, this effect was not affected by starched differing in GI. In addition, inclusion of antioxidants in the diets of high GI fed mice did not have any effect on oxidative and anti-oxidative enzyme gene expression. Thus we conclude from these studies that GI of dietary carbohydrates does not have an effect on the generation of oxidative stress in normal mice.
Publications
- Colbert, KE. 2007. Influence of Dietary Starches Differing in Glycemic Index on Pro-Oxidant and Anti-Oxidant Gene Expression and Insulin Senstivity in a Mouse Model. Master's Thesis, Auburn University, Auburn, AL.
- Huggins KW, Colbert KE. Dietary glycemic index does not influence prooxidant and antioxidant gene expression in adipose tissue of C57BL/6 mice. FASEB Journal 22: 1088.6, 2008
|
Progress 01/01/07 to 12/31/07
Outputs
During Year 2 of this project, we have completed dietary studies of the effects of high versus low glycemic index carbohydrate source on mice in a low fat dietary setting. In addition, during Year 2, we initiated studies on how glycemic index is influenced in the presence of a high fat diet. Mice were fed a low glycemic or high glycemic index diet with 35% of calories from fat. The overall goal of the project is to determine if a high glycemic diet induces oxidative stress and inflammation in mice and that consumption of a low glycemic index diet will prevent these increases in oxidative stress and inflammation. This is critical to human health because increased oxidative stress
Impacts
We found that mice consuming the high GI diet had increased adiposity compared to mice fed the low GI diets. These results, taken together, suggest that consumption of a high GI diet causes increased deposition of adipose tissue mass. This result is consistent with the previous literature dealing with the effects of GI on adipose tissue mass.There were no differences in plasma adiponectin, glucose, and insulin levels in these mice. Based on these results, we concluded that there were no overall differences in insulin sensitivity between the two diet groups. Since consumption of high GI diets result in increased postprandial hyperglycemia, we wanted to investigate the effects of GI on oxidative stress in adipose tissue. We have completed our gene expression analysis of the pro-oxidative enzyme, NADPH oxidase, and the anti-oxidant enzymes (superoxide dismustase, catalase, glutathione peroxidase). There were no differences in expression of these genes between the high GI
and low GI diet groups. These results indicate that GI does not affect oxidative stress status in the adipose tissue. We conclude that, while high GI diets increased adipose tissue mass, generation of oxidative stress in the adipose tissue is not a mechanism by which high-GI diets elicit this effect. High fat diets have been shown to induce systemic and adipose tissue specific increases in oxidative stress. However, our study is the first to address the type of carbohydrate on oxidative stress. As expected, high fat diet feeding significantly increased the expression of the pro-oxidant enzyme NADPH oxidase and significantly lowered the expression of the anti-oxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase in the adipose tissue. However, there were no significant differences between the high GI and low GI diet groups with high fat feeding.In addition, the high fat diets significantly increased plasma levels of IL-6 and TBARS compared to low fat diets. There
were no differences in these plasma metabolites between high GI and low GI animals. These results indicate that while a high fat diet increased the development of insulin resistance and generated increased adipose tissue and systemic oxidative stress, this effect was not affected by starched differing in GI. Thus we conclude from these studies that GI does not have an effect on the generation of oxidative stress in normal mice.
Publications
- Colbert, KE. 2007. Influence of Dietary Starches Differing in Glycemic Index on Pro-Oxidant and Anti-Oxidant Gene Expression and Insulin Senstivity in a Mouse Model. Master's Thesis, Auburn University, Auburn, AL.
|
Progress 01/01/06 to 12/31/06
Outputs
Mice were fed either a high glycemic (Amioca) or low glycemic (Hi-Maize or Hylon V) diet for 16 weeks. We found that mice consuming the high GI diet have increased adiposity compared to mice fed the low GI diets. There were no differences in body weight between the high GI diet and the low GI Hylon group. This indicates that the decrease in adiposity in the Hylon-fed mice was not due to differences in overall body weight. However, there was a small but significant decrease in body weight between the low GI Hi-Maize group compared to the other two groups. Additional studies need to be performed to address if this difference in body weight is due to decreased caloric consumption in these mice. Plasma leptin levels were increased in the high GI Amioca group compared to the two low GI-fed mice. Both of these results, taken together, suggest that consumption of a high GI diet causes increased deposition of adipose tissue mass. There were no differences in plasma
adiponectin, glucose, and insulin levels in these mice. These results along with the glucose and insulin tolerance tests show no overall differences in insulin sensitivity between the diet groups. Overall, while there were significant changes in adipose tissue mass in the high GI animals, there were no overall differences in insulin sensitivity (in the fasted state) between the three diet groups. To address systemic oxidative stress levels in these mice, we measured plasma levels of TBARS and 8-iso-prostaglandin F2α (at the request of the reviewers of the grant). There were no significant differences in these two oxidative stress markers between the three diet groups. However, the values for the 8-iso-prostaglandin F2α were hardly detectable in the plasma so that the validity and reliability of the assay is suspect. According to the literature, the preferred way to measure 8-iso-prostaglandin F2α is in the urine because it is considered more stable and prone to less
degradation than plasma 8-iso-prostaglandin F2α. We did not collect urine from these mice in our first study. Therefore, we will attempt to measure the 8-iso-prostaglandin F2α levels in the urine of these mice in Year 2. We will also include a high fat diet group to serve as a positive control since high fat feeding has been shown to increase 8-iso-prostaglandin F2α levels in mouse urine. Oxidative stress in the adipose tissue was assessed by measuring the gene expression of several antioxidant enzymes and those involved in generating reactive oxygen species. To date, we have analyzed the expression of superoxide dismutase (SOD) and NAPH oxidase in adipose tissue of 5 mice from each diet group. Interestingly, we saw decreased expression of SOD and increased expression of NADPH oxidase in the high GI compared to the low GI groups. However, these results did not reach significance (p = 0.073). Also, the data suggests that there might be a direct correlation between the
expression of the pro-oxidative stress enzyme NADH oxidase and adiposity in the high GI group. These results indicate that increased adipose tissue mass may result in increased oxidative stress in this tissue.
Impacts
The results from our study indicate that consumption of low glycemic starch reduce adiposity in mice compared to high glycemic starch. These results demonstrate that the type of carbohydrate consumed in the diet can have profound metabolic consequences on the body. Understanding the mechanism(s) by which these diets influence whole body glucose metabolism and insulin sensitivity are critical in desgining nutritional therapies for individuals suffering from obesity and diabetes.
Publications
- No publications reported this period
|
|