Progress 10/01/11 to 09/30/16
Outputs
Target Audience:This project is basic research with the scientific community (researchers, graduate students, postdoctoral fellows) as the target audience. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?One PhD students trained under this project. These students were involved in the studies described above. Professional development opportunities for these students were in the form of presentations at regional and national meetings to present their research findings. How have the results been disseminated to communities of interest?Results from this research project were presented at regional and national scientific meetings and in the form of journal atticles and PhD dissertation. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Obesity and type 2 diabetes are major public health problems in the United States. Consumption of dietary fat plays a role in risk factors associated with the development of these conditions. Omega-3 fatty acid consumption may play a protective role but the exact molecular mechanisms of how omega-3 fatty acids consumption may limit the development of obesity and type 2 diabetes is currently not known. We have studied the influence of an n-3 botantical fatty acid, stearidonic acid (SDA). We hypothesized that this fatty acid will act as a surrogate for the n-3 PUFA found in fish oil in the prevention of adiposity, inflammation, and insulin resistance associated with obesity and diabetes. We use a cell culture model approach to determine the effects of SDA on adiposity, inflammation and insulin resistance. In addition, we completed studies assesing the effects of SDA on neuronal cells. For the adiposity studies, we showed that there was a dose-dependent decrease in adipogenesis with cells exposed to increasing amounts of SDA. Similar results were seen with DHA and EPA fatty acids. These fatty acids are the main fatty acids associated with fish oil. It appears that this decrease in adipogenesis was due to decreased expression of lipid-accumulating genes in the adipocytes. These results indicate that SDA has anti-obesity properties and provides similar effects as DHA and EPA. For the inflammation studies, the RAW264.7 macrophage cell line was utilized to assess the role SDA plays in inflammation. Inflammation has been shown to be a causative agane in the development of many chronic conditions. Our studies showed that SDA reduces inflammation in this model. This was achieved through reduction in TLR4 and NF-kappa B activation leading decreased inflammation in these cells. Similar results on inflmmation were also seen in neuronal cells treated with SDA. In addition, work in neuronal cells showed that oxidative stress was reduced in these cells with SDA treatment. Similar effects were seen with DHA and EPA fatty acids. These results suggest that SDA can be effective in reducing adiposity, inflammation and oxidative stress. In addition, SDA appears to behave in a similar manner as the fish oil fatty acids, DHA and EPA. This indicates that SDA may be a more sustainable omega-3 fatty acid source compared to fish oil. This research provides mechanistic data to provide proof-in-prinicple concepts for designing human intervention feeding studies of SDA in treatment and/or prevention of obesity, diabetes, heart disease and Alzheimer's disease.
Publications
- Type:
Theses/Dissertations
Status:
Published
Year Published:
2016
Citation:
Li, Y. (Major Professor: Huggins KW) The protective effects of stearidonic acid on adipogenesis and neurotoxicity (PhD dissertation)
Auburn University, 2016
- Type:
Journal Articles
Status:
Submitted
Year Published:
2017
Citation:
Yueru Li, Yinghui Rong, Ben Nie, Chen Zheng, Rajesh Amin, Robert D. Arnold, Ramesh B. Jeganathan, Kevin W. Huggins. Suppression of adipocyte differentiation and lipid accumulation by stearidonic acid in 3T3-L1 cells. Journal article; Submitted
Yueru Li, Yinghui Rong, Ben Nie, Chen Zheng, Rajesh Amin, Robert D. Arnold, Ramesh B. Jeganathan, Kevin W. Huggins. Suppression of adipocyte differentiation and lipid accumulation by stearidonic acid in 3T3-L1 cells. Journal article; Submitted
Yueru Li, Yinghui Rong, Ben Nie, Chen Zheng, Rajesh Amin, Robert D. Arnold, Ramesh B. Jeganathan, Kevin W. Huggins. Suppression of adipocyte differentiation and lipid accumulation by stearidonic acid in 3T3-L1 cells. Journal article; Submitted
Yueru Li, Yinghui Rong, Ben Nie, Chen Zheng, Rajesh Amin, Robert D. Arnold, Ramesh B. Jeganathan, Kevin W. Huggins. Suppression of adipocyte differentiation and lipid accumulation by stearidonic acid in 3T3-L1 cells.
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Progress 10/01/14 to 09/30/15
Outputs
Target Audience:This project is basic research with the scientific community as the target audience. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?One PhD student (Yueru Li) is currently being trained under this project. The student has been involved in the cell culture studies described above. How have the results been disseminated to communities of interest?Results from these research studies have been presented at regional scientific meetings. What do you plan to do during the next reporting period to accomplish the goals?We will continue assessing the effects of omega-3 fatty acids on neuronal cell function as they relate to specifc markers related to Alzheimer's disease.
Impacts
What was accomplished under these goals?
We initiated studies in the current year on the effcts of SDA and other omega-3 fatty acids on neuronal cell inflammation, oxidative stress and insulin signaling. Initial studies were carried out to assess the incorporaton of omega-3 into a cell cultue model for neuronal cells. Incorporation of omega-3 fatty acids SDA, DHA, EPA and ALA were quantified using GC analysis. These fatty acids were incorporated into cells at similar rates and maximized within 24 hours. Inflammation studies were carried out using the above mentioned omega-3 fatty acids to assess their effects on cellular inflammation and oxidative stress. The omega-3 fatty acids DHA, EPA and SDA were shown to reduce cellular inflammation induced by LPS. ALA was unable to reduce LPS-induced inflammation. Inflammation was assessed by gene expression analysis of the pro-inflammatory cytokines IL-6 and TNF-alpha. Additonal studies were carries out to assess the effects of these omega-3 fatty acids on oxidative stress. Oxidative stress was induced by hydrogen peroxide. Oxidative stress was not shown to be reduced with these omega-3 fatty acids. In addiiton, oxidative stress generated by amyloid beta protein was not shown to be reduced by these omega-3 fatty acids. Results from the Insulin signalng studies are still be analyzed.
Publications
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Progress 10/01/13 to 09/30/14
Outputs
Target Audience: This project is basic research with the scientific community as the target audience. Project results have been reported to the scientific community at regional professional meetings. Preliminary results for the reporting period were presented at the Boshell Diabetes Research Day at Auburn University. Changes/Problems: We have included some additional studies not outlined in the original project proposal. These are similar technqiues and studies that we are already conducting as part of this project. We have initiated studies in collaboation with Dr. Ramesh Jeganathan (Assistant Professor, Dept. of Nutrition, Auburn University) on the effects of SDA on inflammation and oxidative stress in neuronal cells. Once the mouse studies are completed, we will also assess similar outcomes in brain tissue of these mice. This may be important for preventing the development of various neurodegenerative conditions such as Alzheimer's Disease. As outlined i nthe Accomplishments section, our initial mouse studies were limited in duration due to availability of SDA oil for diet feeding studies. This appears to not be a problem for future studies so that we are able to proceed as planned in the original project outline. What opportunities for training and professional development has the project provided? One PhD student (Yueru Li) is currently being trained under this project. The student has been involved in the cell culture studies described above and is currently overseeing the day to day activities of the mouse feeding studies. How have the results been disseminated to communities of interest? Results from these research studies have been presented at the 7th Annual Boshell Diabetes Research Day at Auburn University. A maunscript is currently under revision for publication based on the cell culture studies described above. What do you plan to do during the next reporting period to accomplish the goals? We plan to continue with the cell culture and mouse feeding studies described above for the next reporting period. In addition, we are planning to continue work on the SDA effects on neuronal inflammation and oxidative stress in collaboration with Dr. Ramesh Jeganathan (Auburn University).
Impacts
What was accomplished under these goals?
Stearidonic acid (SDA) is a botanical n-3 polyunsaturated fatty acid (PUFA) that may have similar health benefits to n-3 PUFA found in fish oil. Our overall goal is to assess the benefits of SDA in the prevention and/or treatment of obesity and diabetes. 1)We have completed studies related how SDA inlfuences adipogenesis in a cell culture model system using 3T3-L1 cells. These studies showed tha there is a dose-dependent decrease in adipogenesis with cells exposed to increasing amounts of SDA. Similar results were seen with DHA and EPA. We have initiated studies using pre-adipocytes isolated from mouse adipose tissue. Using these cells, we will conduct similar experiments described above to determine if similar results are found in ex vivo cells. We are currently learning how to isolate these cells from mouse adipose tissue. 2) to determine in the influence of SDA on inflammation. We have previously shown that SDA decreases LPS-induced inflammation in a cell culture model system using RAW264.7 and 3T3-L1 cells. Our studies in this reporting period has shown that SDA reduces TLR4 and NF-kappa B activation leading to decreased inflammation within these cells. This suggests a possible mechanism by which SDA is exerting its anti-inflammatory effects. 3) to determine the in vivo effects of dietary SDA on adiposity, inflammation, and insulin sensitivity in a mouse model. Initial mouse studies were incomplete due to limited availabity of SDA-enriched oil from commerical sources. Our limited feeding studies (4 weeks) showed that SDA-fed mice on a high fat diet were not significantly different compared to control high fat diet-fed mice in terms of body weight, adiposity, glucose, insulin and leptin levels. Triglyceride levels were reduced in the SDA-fed mice compared to control mice; however, these results were not statistically significant. Longer term feeding studies are currently being repeated in our lab.
Publications
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Progress 01/01/13 to 09/30/13
Outputs
Target Audience: This project is basic research with the scientific community as the target audience. Project results have been reported to the scientific community at regional professional meetings. Preliminary results for the reporting period were presented at the Boshell Diabetes Research Day at Auburn University. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? One PhD student (Yueru Li) is currently being trained under this project. The student has been involved in the cell culture studies described above and is currently overseeing the day to day activities of the mouse feeding study. How have the results been disseminated to communities of interest? Results from these research studies have been presented at the 6th Annual Boshell Diabetes Research Day at Auburn University and a manuscript has been submitted for the cell culture work described above. What do you plan to do during the next reporting period to accomplish the goals? We plan to continue with the mouse feeding studies for the next reporting period.
Impacts
What was accomplished under these goals?
Stearidonic acid (SDA) is a botanical n-3 polyunsaturated fatty acid (PUFA) that may have similar health benefits to n-3 PUFA found in fish oil. Our overall goal is to assess the benefits of SDA in the prevention and/or treatment of obesity and diabetes. 1) to determine the effect on SDA on adipogenesis. During the reporting period, we conducted experiments on how SDA influences adipogenesis in a cell culture model system using 3T3-L1 cells. We confirmed that there is a dose-dependent decrease in adipogenesis with cells were exposed to increasing amounts of SDA. These results were similar to what was obtained with DHA and EPA, common n-3 PUFA found in fish oil. This effect was mainly due to a decrease in the expression in transcription factors that control lipid accumulation in these cells. This data suggests that SDA may be benefical in terms of reducing the amount of lipid accumulating in adipose tissue. 2) to determine in the influence of SDA on inflammation. During the reporting period, we conducted experiments on how SDA infleunces inflammation in a cell culture model system using RAW 264.7 and 3T3-L1 cells. SDA was capable of decreasing LPS-induced inflammation to a similar extent as DHA and EPA. This was confirmed by measuring the expression of the known pro-inflammatory cytokines, TNF-alpha and interleukin-6 gene expression. By decreasing inflammation, SDA may be shown to decrease inflammatory-assciate conditions such as obesity and diabetes. 3) to determine the in vivo effects of dietary SDA on adiposity, inflammation, and insulin sensitivity in a mouse model. We have established diet composition for these studies and recieved approval from IACUC to conduct these studies. These studies are currently underway in our lab.
Publications
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Progress 01/01/12 to 12/31/12
Outputs
OUTPUTS: This project is basic research with the scientific community as the target audience. Project results have been reported to the scientific community at regional professional meetings. Preliminary results for the reporting period were presented at the Boshell Diabetes Research Day at Auburn University. This project has provided training for one PhD student and one Master's student. PARTICIPANTS: This project is overseen by the PI, Kevin Huggins. During the reporting period, Dr. Raj Amin (Pharmacal Sciences, Auburn University) has collaborated with Dr. Huggins on this project. This project involved training one PhD student (Rong, Y.) and is currently training one Master's student (Li, Y.) during the reporting period. TARGET AUDIENCES: This project's target audience is the basic science community. Ultimately, recommendations on SDA consumption could be made to the general public from this research. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
This project focuses on the impact of the botanical omega-3 fatty acid stearidonic acid (SDA) and its impact on adipogenesis and inflammation. We have shown in the reporting period that SDA inhibits adipocyte differentiation by decreasing expression of adipogenic transcription factors and adipogenic lipid-accumulation genes in a dose-dependent manner in 3T3-L1 cells. These cells are a common model system used to study adipocyte differentiation. SDA also inhibited triglyceride accumulation in a dose-dependent manner. Similar effects were see with the omega-3 fatty acids DHA and EPA. The omega-3 fatty acid, ALA, did not inhibit adipocyte differentiation of 3T3-L1 cells to the same extent as SDA. Studies on the impact of SDA on inflammation in RAW264.7 macrophages have also been initiated during the reporting period. We have shown that SDA inhibits LPS-induced inflammation to a similar extent as fish-oil omega-3 fatty acids (DHA and EPA). SDA decreased gene expression of tumor necrosis factor-alpha and interleukin-6. We are currently deciphering if this inhibitory effect on inflammation is dependent on TLR4 activity. Based on these preliminary results, SDA may have similar biological effects to fatty acids found in fish oil and thus may be a useful surrogate for fish oil in treating obesity-related conditions. Based on these results, a grant was submitted to the Diabetes Action Research and Education Foundation and funded for 2013.
Publications
- Rong, Y.(Major Professor: Huggins KW) The effects of stearidonic acid on 3T3-L1 adipocytes PhD dissertation) Auburn University, 2012.
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