Progress 09/15/06 to 08/31/09
Outputs
OUTPUTS: The NWRC/CDFIN approached improving life-long health by addressing both nutritional and activity-related issues, including Vitamin A and iron deficiency and obesity. One project's goal was to enhance iron content in the maize endosperm by overexpressing soybean ferritin gene and to increase iron absorption from transgenic maize seeds. A total of 16 individual transformed lines (T1 seeds) were obtained from transformations with A188lpa1, and 3 from A188. The transgenic A188lpa1-1 maize lines show a significant increase in iron bioavailability compared to both the A188 nontransgenic control and the A188 transgenic line. The animal subjects of another project never developed metabolic symptoms as expected due to a couple of reasons, so the goals of the project could not be addressed. Another study examined the C-reactive protein (CRP) and fibrinogen, which are established atherosclerotic cardiovascular disease risk factors that may be elevated in obesity. It was determined that overall adiposity or centrally-located fat assessed via dual-energy X-ray absorptiometry (DXA) was related to these inflammatory markers in 242 healthy postmenopausal women. In a study using mice as experimental animals, it was shown that mitochondrially targeted vitamin E with three carbons in the alkyl connecting chain (MitoVit E3) can decrease mitochondrial oxidative stress and decrease obesity in mice possibly through enhancing fatty acid oxidation. Another study used mice to examine relationships among dietary fat and inflammation in adipose and muscle. Measuring body weight and fat pad weights and varying fat content in diet, results show the Tlr-4 mutant mice had significantly lower weights when compared to wild-type mice lacking functional Tlr-4 receptors. Researchers hypothesized that antibacterial and anti-inflammatory efficacies of food phenolics may be inhibited by phenolic degrading microbes, varying the abilities to prevent periodontal disease. Antibacterial activities of 7 food flavonoids screened against several model human periodontal pathogens were negligible, however food extracts associated with these flavonoids showed antipathogen activity. A mixture of flavonoids were incubated with human saliva (n = 20 subjects) and concentrations of phenolics were assessed by HLPC. Another study demonstrated that Vitamin A status and/or supplementation can directly alter the regulation of iron homeostasis at a posttranscriptional level. This new knowledge will be of tremendous benefit for dietary strategies and therapies directed at preventing or minimizing anemia and its complications. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The purpose of one project is to significantly improve the bioavailability of iron from maize, which in turn, will greatly help to improve the process of combating iron-deficiency anemia around the world. Thus, a successful completion of the project will have a far-reaching impact on the food biofortification process. The results of another study indicated that centralized fat mass and hip fat mass, respectively, contributed significantly to CRP and fibrinogen. Further study is warranted to determine the responsiveness of these acute phase proteins to loss of body fat through exercise and dietary intervention. The data from a study of Mitochondrially targeted vitamin E with three carbons in the alkyl connecting chain (MitoVit E3) suggests that MitoVit E3 has anti-obesity effects by mitigating oxidative stress. The concept could have implications for use in humans. The species of the Actinomycetales Order (Streptomyces coelicolor and Streptomyces avermitilis) and Lactobacillus brevis/Lactobacillus reuteri may play a significant role in human oral cavity degradation of caffeic acid and rutin, respectively, and might influence approaches to preventing oral disease and inflammation. Our incomplete understanding of the mechanisms relating obesity, metabolic syndrome, and PCOS, hinders the prevention and efficient/effective treatment of these diseases. Data provided from the proposed experiment is expected to facilitate development of methodologies that may preclude the development of diseases associated with obesity such as metabolic syndrome and PCOS. Iron and vitamin A deficiency remains a significant problem for millions of people worldwide. Thus, understanding how these two essential nutrients modulate each other's homeostasis is an important avenue towards developing intervention protocols designed to optimize health. Tlr-4 receptors, known to recognize bacterial components, are also able to recognize certain dietary fatty acids. One project has provided evidence that the loss of a functional Tlr-4 receptor protects mice from obesity caused by a high saturated fat diet. Chemical dephosphorylation is shown to be effective in reducing Fe binding of the phosvitin, and cell uptake of Fe is improved by such treatment.
Publications
- Bhupathiraju SN, Alekel DL, Stewart JW, Hanson LN, Shedd KM, Reddy MB, Hanson KB, Van Loan MD, Genschel U, Koehler KJ. Relationship of circulating total homocysteine and C-reactive protein to trabecular bone in postmenopausal women. J Clin Densit 10(4):395-403, 2007.
- Mao, G. G. A. Kraus, I. Kim, M. E. Spurlock, T. B. Bailey, P. M. Dixon, Q. Zhang, and D. C. Beitz. 2009. Mitochondrially targeted vitamin E normalizes hepatic mitochondrial oxidative stress and inhibits fat deposition in mice. Submitted to J. Nutr.
- Perry CD, Alekel DL, Ritland L, Bhupathiraju SN, Stewart JW, Hanson LN, Matvienko O, Kohut M, Reddy MB, Van Loan MD, Genschel U. Relationship of centrally-located body fat to inflammatory markers in healthy postmenopausal women. Menopause 15(4):619-627, 2008.
- Schroeder, S.E., Reddy, M.B. & Schalinske, K.L. (2007) Retinoic acid modulates hepatic iron homeostasisin rats by attenuating the RNA-binding activity of iron regulatory proteins. J. Nutr., 137: 2686-2690.
- Shedd KM, Hanson KB, Alekel DL, Schiferl DJ, Hanson LN, Van Loan MD. Quantifying leisure physical activity and its relation to bone density and strength. Med Sci Sports Exerc. 39(12):2189-2198, 2007.
- Ye Z, Rieser E, Li L, Hendrich S. (2009). Identification of Bacterial Species with Phenolic-degrading activity in the Human Oral Cavity, FASEB J. 23:345.6.
- Ye Z. 2009. Metabolism of Herbal Phenolics in Gut/Oral Microbiota or Caco-2 Cells and Bioavailability Associated Efficacy of Caffeic Acid in Mouse Colitis. Dissertation, Iowa State University Library, Ames, IA.
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Progress 09/15/07 to 09/14/08
Outputs
OUTPUTS: Multiple approaches were used in CDFIN's effort to promote life-long health through nutrition. In a study of the response of C-reactive protein and fibrinogen to soy isoflavones in postmenopausal women, overall adiposity or centrally-located fat assessed via dual-energy X-ray absorptiometry (DXA)were related to these inflammatory markers in 242 healthy postmenopausal women. In a study to increase iron absorption from transgenic maize seeds by using a low phytic acid mutant of maize for generation of transgenic maize, a total of 16 individual transformed lines (T1 seeds) were obtained from transformations with lpal, and 3 from A188. Two pilot studies were completed in a project to examine the impact of a mitochondrial targeted vitamin E on oxidative stress and obesity development. In studying a novel nutritional protocol for protection of health status of humans with nonalcoholic fatty liver disease (NAFLD) using rats as a model, liver samples were analyzed for liquid and triacylglycerol content. Carcasses were ground and analyzed for dry matter, lipid, and protein content. Food phenolics may vary in their ability to protect against periodontal disease because their antibacterial and anti-inflammatory efficacies may be inhibited by phenolic degrading microbes. Antibacterial activities of 7 food flavonoids screened against several model human periodontal pathogens were negligible. A mixture of rutin, caffeic acid, daidzein, quercetin, naringenin, luteolin and myricetin was incubated with 20 subject's human saliva and concentrations of phenolics were assessed by HLPC. Dissemination of data on the study of regulation of inflammation in adipose tissue and skeletal muscle by dietary fatty acids and adiponectin was presented at the Experimental Biology Meeting in Washington, D.C. in 2007. Using a rat model, research on modulation of iron homeostasis by Vitamin A has shown that administration of retinoic acid, divergently modulates that hepatic expression of two key proteins involved in iron homeostasis: the abundance of ferritin, a storage protein for iron was increased, whereas a decrease in transferrin receptor, a membrane protein responsible for cellular uptake of iron. In another study the relationships among dietary fat and inflammation in adipose and muscle of mice were examined. Body weight and fat pad weight were measured, and markers of inflammation, such as macrophage infiltration into adipose tissue, were also evaluated. Dissemination of research by students and their mentors occurred at local, state, and national workshops, symposia, and conferences, including the Federation of American Societies for Experimental Biology, North American Menopause Society (NAMS), Iowa Academy of Science, American Egg Board, Iowa Egg Council and the Consortium for Plant Biotechnology Research (CPBR). PARTICIPANTS: Primary Investigators: Lee Alekel, Maneesha Aluru, Donald Beitz, Patricia Murphy, Carolyn Komar, Kevin Schalinske, Michael Spurlock, Tong Wang; Co-Primary Investigators: Oksana Matvienko, Marta Van Loan, Jeanne Stewart, Kathy Hanson, Ulrike Genschel, Ken Koehler, Manju Reddy, Walter Hsu, Suzanne Hendrich, George Kraus, Kim Brogden; Graduate students: Portia Allen, Shilpa Bhupathiraju, Courtney Perry, Dane Goede, Anthony Young, Benjamin Noack, Caleb Grote, Michelle Bohan Brown, Andrew Brown, Mohamed Osman, Gaowei Mao, Ying Zhou, Sophie Joly, Undergraduates: Erinn Rieser In total, more than 20 graduate and undergraduate students were provided support and valuable research experiences that were the basis for advanced training or masters/doctoral theses for several. Dissemination of research by students and their mentors occurred at local, state, and national workshops, symposia, and conferences, including the Federation of American Societies for Experimental Biology, North American Menopause Society (NAMS), Iowa Academy of Science, American Egg Board, Iowa Egg Council and the Consortium for Plant Biotechnology Research (CPBR). TARGET AUDIENCES: Targeted audiences included those with peridontal disease; postmenopausal women; individuals with Iron and Vitamin A deficiency; obese men and women; scientists; medical and food industry professionals. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
In evaluating the response of C-reactive protein (CRP) and fibrinogen to soy isoflavones in postmenopausal women, results indicated that androidal fat mass and hip fat mass, respectively, contributed significantly to CRP and fibrinogen. The study on overexpression of Ferritin in Low-Phytate Maize to improve Iron content and bioavailability, surmize that iron deficiency anemia is one of the most common nutritional deficiencies, resulting in significant socio-economic losses. This project will have a far-reaching impact on the food biofortification process. At the conclusion of data analysis on a novel nutritional protocol for protection of health status of humans with nonalcoholic fatty liver disease (NAFLD) using rats as a model, if it is demonstrated that the nutraceuticals used in this study positively impacted the health of the rats utilized, it could potentially impact how patients with non-alcoholic fatty liver disease are medically managed. These nutraceuticals could possibly be prescribed in place of, or in addition to, the pharmaceuticals commonly used today. It was determined in the screening systems for food flavonoids as candidate agents in preventing periodontal diseases that food phenolics may vary in their ability to protect against periodontal disease because their antibacterial and anti-inflammatory efficacies may be inhibited by phenolic degrading microbes. Antibacterial activities of 7 food flavonoids screened against several model human periodontal pathogens were negligible, however food extracts associated with these flavonoids showed antipathogen activity, supporting the need for further work to identify these factors. It was clearly demonstrated that Vitamin A status and/or supplementation can directly alter the regulation of iron homeostasis at a posttranscriptional level in the study of modulation of Iron homeostatis by Vitamin A: Implications for Vitamin A-deficiency anemia. The project regulation of inflammation in adipose tissue and skeletal muscle by dietary fatty acids and adiponectin provided evidence that the loss of a functional Tlr-4 receptor protects mice from obesity caused by a high saturated fat diet. The recent recognition of mitochondrial dysfunction related diseases as a result of overproduction of reactive oxygen species has drawn awareness to the need to develop antioxidants targeted to mitochondria. MitoVitE could be a potential candidate for this new therapy. Modification of egg yolk protein for improved Iron bioavailability has shown that chemical dephosphorylation is effective in reducing Fe binding of the phosvitin, and cell up-take of Fe is improved by such treatment.
Publications
- Zhong Y, Rieser E, Li L, Hendrich S. (2009). Identification of Bacterial Species with Phenolic-gegrading activity in the Human Oarl Cavity, FASEB J, abstract in press.
- Davis, J. E., Gabler, N. K., Walker-Daniels, J. and Spurlock, M. E.(2008). Tlr-4-deficiency selectively protects against obesity induced by diets high in saturated fat. Obesity 16(6): 1248-55.
- Mao, G., Kraus, G., Spurlock, M., and Beitz, D. 2008. Mitochondrially targeted vitamin E decreases diet-induced fat deposition in C57BL/6 mice through normalizing mitochondrial oxidative stress and function. 2009 Experimental Biology meeting.
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Progress 09/15/06 to 09/14/07
Outputs
OUTPUTS: Multiple approaches are being taken in CDFIN's effort to promote life-long health through nutrition. In a study of the response of C-reactive protein and fibrinogen to soy isoflavones in postmenopausal women, dual-energy X-ray absorptiometry was used to assess overall and regional body composition to determine wither centrally-located fat and/or overall adiposity were related to these inflammatory markers in healthy postmenopausal women. Scientists are examining the novel interaction between vitamin A, iron and folate. Two pilot studies have been completed in a project to examine the impact of a mitochondrially targeted vitamin E on oxidative stress and obesity development. Saliva samples have been collected and preliminary data regarding oral microbial degradation rates have been generated for additional study of screening systems for food flavonoids as candidate agents in preventing periodontal disease. A project studying effects of gemfibrozil, metformin, rosiglitazone,
taurine, and alpha-tocopherol on the prevention of nonalcoholic fatty liver disease has completed the first phase of activity and results of tissue and plasma sample analysis will be completed and reported in the next activity period. Initial generation of transgenic maize plants has been completed and T2 generation seeds will be the target of further analyses for increased iron content and bioavailability. In total, more than 20 graduate and undergraduate students were provided support and valuable research experiences that were the basis for advanced training or masters/doctoral theses for several. Dissemination of research occurred at local, state, and national workshops, symposia, and conferences, including the Federation of American Societies for Experimental Biology, North American Menopause Society (NAMS), Iowa Academy of Science, American Egg Board, Iowa Egg Council.
PARTICIPANTS: In total, more than 20 graduate and undergraduate students were provided support and valuable research experiences that were the basis for advanced training or masters/doctoral theses for several. Dissemination of research by students and their mentors occurred at local, state, and national workshops, symposia, and conferences, including the Federation of American Societies for Experimental Biology, North American Menopause Society (NAMS), Iowa Academy of Science, American Egg Board, Iowa Egg Council.
Impacts
In an evaluation of the relationships among dietary fat, adiponectin and inflammation in adipose tissue and skeletal muscle indicates androidal fat mass and hip fat mass, respectively contributed significantly to C-reactive protein and fibrinogen. The results provide the foundation for further study to determine the responsiveness of these acute phase proteins to loss of body fat through exercise and dietary intervention in postmenopausal women. Additionally, results suggest a weak but negative relationship between homocysteine and trabecular bone. Further study is needed to examine the relationship of hyperhomocysteinemia and elevated C-reactive protein to trabecular bone loss and the response of trabecular bone to dietary intervention. In a project evaluating nutritional regime and drug/neutraceutical treatments for prevention of nonalcoholic fatty liver disease (NAFLD), statistical analysis of data is underway, and expected impact is that the research will provide
basic information that will be applicable to decreasing the incident of NAFLD in humans. Chemical dephosphorylation of egg yolk protein (50-65% removal of phosphorus) and demonstrated increase of iron absorption using cell lines (up to 3 times higher iron absorption compared to dephosphorylated protein) should provide the egg industry with a valuable and novel processing approach for producing nutritionally enhanced egg protein co-product could potentially generate multiple value-added products to make the yolk fractionation process feasible and profitable. Ongoing data analysis in a study of food flavonoids as candidate agents in preventing periodontal disease may potentially lead to the development of novel products for oral hygiene. Results of a project targeting transgenic maize seeds obtained in the current reporting period for further analyses and to identify lines with increased iron content and bioavailability will be of significant importance in optimizing the health of
people worldwide, as will the research conducted to advance understanding of the novel interaction between vitamin A, iron, and folate.
Publications
- Bhupathiraju, S.N., Alekel, D.L., Stewart, J.W., Hanson, L.N., Shedd, K.M., Reddy, M.B., Hanson, K.B., Van Loan, M.D., Genschel, U., Koehler, K. J. 2007. Relationship of circulating total homocysteine and C-reactive protein to trabecular bone in postmenopausal women. J Clin Densit 10(4):395-403.
- Perry, C.D., Alekel, D.L., Ritland, L., Bhupathiraju, S.N., Stewart, J.W., Hanson, L.N., Matvienko, O., Kohut, M., Reddy, M.B., Van Loan, M.D., Genschel, U. 2007. Relationship of centrally-located body fat to acute phase proteins and proinflammatory cytokines in healthy postmenopausal women., Menopause 15(4), in press.
- Schroeder, S.E. and Schalinske, K.L. 2006. Interaction between vitamin A status and iron homeostasis is mediated by iron regulatory proteins. FASEB J. 20:A1315.
- Schroeder, S.E., Reddy, M.B., and Schalinske, K.L. 2007. Retinoic acid modulates hepatic iron homeostatis in rats by attenuating the RNA-binding activity of iron regulatory proteins. J. Nutr., 137: 2686-2690.
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