Progress 02/01/14 to 01/31/19
Outputs
Target Audience:scientists, general public, health care professionals, specialty crop industry, food industry Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?One graduate student (Master's degree) and more than 6 undergraduate students and interns have participated in this study during the course of 5 year study period. How have the results been disseminated to communities of interest?The results are being analyzed for publication in scientific journals. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Dietary intervention study with docosahexaenoic acid (DHA) and blueberry powder has been completed with a total of 62 subjects completed the study. The results are being analyzed for publication in scientific journals.
Publications
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Progress 02/01/17 to 01/31/18
Outputs
Target Audience:General public, scientific community, health care professionals, food industry, specialty crop industry Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Our clinical dietary intervention study provided learning opportunity to graduate students and research associates for all aspects of intervention study including subject recruitment, screening procedure, preparation of consent form, preparation of experimental diets, samples analyses and data analyses. How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?To complete analysyes of samples for all outcome measurements (i.e, plasma cytokines), data analyses and manuscript preparation, no-cost extension for 12 month has been requetsed. During this time, we plan to complete analyses of samples,data analyses and preparation of manuscript for publication
Impacts
What was accomplished under these goals?
Dietary intervention study proposed in the grant proposal has been completed in November, 2017; a total of sixty subjects as proposed have been completed for the intervention study with blueberry powder ordocosahexaenoic acid supplementation (including placebo control). However, to complete analysyes of samples for all outcome measurements (i.e, plasma cytokines), data analyses and manuscript preparation, no-cost extension for 12 month has been requetsed.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
1) Hwang DH, Kim JA, Lee JY, Mechanisms for the activation of Toll-like receptor2/4 by saturated fatty acids and inhibition by docosahexaenoic acid. Eur J Pharmacol. 2016 Aug 15;785:24-35. doi: 10.1016/j.ejphar.2016.04.024. Epub 2016 Apr 13
2) Kikumi D. Ono-Moore, Ling Zhao, Shurong Huang, Jeong-a Kim, Jennifer M. Rutkowsky, Ryan G. Snodgrass, Dina A. Schneider, Michael J. Quon, Daniel H. Hwang. Transgenic mice with ectopic expression of constitutively active TLR4 in adipose tissues do not show impaired insulin sensitivity. Immunity, inflammation and diseases doi:10.1002/iid3.162, 2017
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Progress 02/01/16 to 01/31/17
Outputs
Target Audience:general public, scientific comunity, health care professionals, food industry, specialty crop industry Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Three temporary postgraduateresearch scientists were hired and assigned to work for this project. One graduate student is supported and trained. Two undergraduate students (interns) have been trained How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?The first batch of plasma samples from 31 subjects so far completed will be analyzed for cytokines and lipids.Endo-Pat data will also be analyzed.
Impacts
What was accomplished under these goals?
We have so far (January 25, 2017, see details below) completed 31 subjects (60 subjects were proposed to complete). We expect the completion of 60 subjects by the end of 2017. There are two treatment groups (blueberry powder and docosahexaenoic acid) and one placebo group. This is a cross-over design study. Each subject has to go through each treatment diet with 4 weeks washout period between treatment diet. Each subject requires three test day visits. Thus, it takes two months for each subject to complete the study. Personnel from the Human Study Section from our research Center, three research associates, Lab manger and one graduate student have been working on this project. They performed advertisement for recruitment, phone interview, dietary education, scheduling and blood sample analyses. Blood samples were taken by phlebotomist and the screening of blood samples to determine exclusion criteria was done at University of California- Davis Medical Center. Treatment diet and a standardized dinner were prepared at the Metabolic Kitchen in our Research Center. The subjects picked up the dinner prior to the test date. Outcome measurements include plasma insulin, plasma lipid profile including free fatty acids, cytokines and adhesion molecule (CD11b) expression in blood monocytes. Endo-PAT measurement has also been performed to assess endothelial vasodilator function. Human study subjects statistics: Total number of subjects completed: 31 Total number of subjects in progress: 9 Total number of subjects approved to participate thus far but not enrolled yet: 8 Total number of subjects who withdrew from study: 12 Total number of subjects disqualified due to decline to enroll/no response/other reasons: 87 Total number subjects disqualified by phone screen: 88 Total number of subjects disqualified by physical screen: 40
Publications
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Progress 02/01/15 to 01/31/16
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?One graduate student is supported and assigned to this project. Two temporary staff technicians are supported and assigned to this project Two undergraduate students (interns) are trained and participating in this project How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?So far 15 study visit days have been completed. Starting Jannaury, 2016 we will processat least three study visit days per week We will continue this pace of study in 2016. Additional advertisement, screening and scheduling will continue. The first batch of plasma samples willl be analyzed for cytokines and plasma lipids in March 2016 and October, 2016. Endo-Pat measurement values willl also be analyzed.
Impacts
What was accomplished under these goals?
Since our AFRI/NIFA project was approved for funding, we have obtained a supplementary funding from the US Highbush Blueberry Council for a study to evaluate the endothelial vasodilator function using the Endo-PAT assay for the subjects consuming the high fat diet supplemted with blueberry powder. We decided also to perform the Endo-Pat assay for the subjects consuming the high fat diet supplemented with docosahexaenoic acid (DHA) supplementation : the additional cost for this assay for the DHA treatment group will be supplemented from our in-house CRIS project funds. The Endo-PAT 2000 is a new approach to assess endothelial vasodilator function in a rapid non-invasive manner. The technique provides values for the calculation of a Reactive Hyperemia Index (RHI), which gives an indication of the endothelial vasodilator function. The RHI is the post-to-pre occlusion PAT signal ratio in the occluded arm, relative to the same ratio in the control arm, and corrected for baseline vascular tone. Studies using the Endo-PAT have shown that the RHI score reflects NO-bioavailability 25. The RHI correlates with the measurement of endothelial vasodilator function with brachial flow-mediated dilatation (FMD). Subjects with a greater degree of cardiovascular disease exhibit a lower score and values are also lower in other conditions associated with impaired endothelial function and risk of cardiovascular disease. Notably, RHI values appear to be predictive of cardiovascular outcomes. A low RHI (indicating endothelial dysfunction) can be reversed with treatment. Therefore, in the propose study, whether blueberry intake improves impairment of postprandial endothelial function will be investigated using the Endo-PAT assay. The IRB committee raised a question about the potential risk of anemia for the study subjects who will visit our Center for four times for different dietary regimens (placebo, blueberry powder, DHA and a combination of blueberry and DHA) and for blood samples to be taken during each visit. Therefore, we decided to perform first a study with three dietary treatments (placebo,blueberry powder and DHA). The dietary treatment with a combination of blueberry powder and DHA will be performed separately after the first study. 3) In the mean time, we have studied whether cyanidin-O-glucoside (one of the major polyphenols present in blueberries) inhibits inflammasome-mediated monocyte activation in monocytes (specific objective 2). 4) A Jr. Specialist (research associate) has been hired to participate in this project. 5) Revised IRB application was submitted to University of California-Davis.
Publications
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Progress 02/01/14 to 01/31/15
Outputs
Target Audience: Title: Suppression of postprandial monocyte activation by fruit rich in anti-inflammatory polyphenols or docosahexaenoic acid in humans (Project:2013-03477) Specific Objectives: 1) To determine whether high saturated fat diet-induced monocyte activation is suppressed by known dietary inhibitors of pattern recognition receptor (PRR) activation. We will investigate two potential dietary inhibitors: anti-inflammatory polyphenols (strawberry powder as a source of polyphenols) and docosahexaenoic acid (DHA as capsule), and whether a combined mixture of blueberry powder and DHA shows more potent inhibitory effects than strawberry powder or DHA alone in healthy human volunteers. 2) To determine the mechanism by which the high saturated fat diet activates but strawberry powder or DHA supplementation inhibits the monocyte activation. Our hypothesis is that saturated fatty acids derived from the high saturated fat meal activate PRRs (TLR4, TLR2 and inflammasome) leading to the expression of proinflammatory marker gene products including IL-1β in blood monocytes. We will determine first, whether saturated fatty acids derived from the high saturated fat activate TLR2 and TLR4 leading to the expression of pro-IL-1β and inflammasome-mediated IL-1β release, and second, whether the saturated fatty acid-induced monocyte activation is inhibited by DHA or cyanidin-3-O-glucoside, the major polyphenol present in blueberries. Progress Report: 1) Since our AFRI/NIFA project was approved for funding, we have obtained a supplementary funding from the US Highbush Blueberry Council for a study to evaluate the endothelial vasodilator function using the Endo-PAT assay for the subjects consuming the high fat diet supplemted with blueberry powder. We decided also to perform the Endo-Pat assay for the subjects consuming the high fat diet supplemented with docosahexaenoic acid (DHA) supplementation : the additional cost for this assay for the DHA treatment group will be supplemented from our in-house CRIS project funds. The Endo-PAT 2000 is a new approach to assess endothelial vasodilator function in a rapid non-invasive manner. The technique provides values for the calculation of a Reactive Hyperemia Index (RHI), which gives an indication of the endothelial vasodilator function. The RHI is the post-to-pre occlusion PAT signal ratio in the occluded arm, relative to the same ratio in the control arm, and corrected for baseline vascular tone. Studies using the Endo-PAT have shown that the RHI score reflects NO-bioavailability 25. The RHI correlates with the measurement of endothelial vasodilator function with brachial flow-mediated dilatation (FMD). Subjects with a greater degree of cardiovascular disease exhibit a lower score and values are also lower in other conditions associated with impaired endothelial function and risk of cardiovascular disease. Notably, RHI values appear to be predictive of cardiovascular outcomes. A low RHI (indicating endothelial dysfunction) can be reversed with treatment. Therefore, in the propose study, whether blueberry intake improves impairment of postprandial endothelial function will be investigated using the Endo-PAT assay. 2) The IRB committee raised a question about the potential risk of anemia for the study subjects who will visit our Center for four times for different dietary regimens (placebo, blueberry powder, DHA and a combination of blueberry and DHA) and for blood samples to be taken during each visit. Therefore, we decided to perform first a study with three dietary treatments (placebo,blueberry powder and DHA). The dietary treatment with a combination of blueberry powder and DHA will be performed separately after the first study. 3) In the mean time, we have studied whether cyanidin-O-glucoside (one of the major polyphenols present in blueberries) inhibits inflammasome-mediated monocyte activation in monocytes (specific objective 2). Changes/Problems: The IRB committee raised a question about the potential risk of anemia for the study subjects who will visit our Center for four times for different dietary regimens (placebo, blueberry powder, DHA and a combination of blueberry and DHA) and for blood samples to be taken during each visit. Therefore, we decided to perform first a study with three dietary treatments (placebo,blueberry powder and DHA). The dietary treatment with a combination of blueberry powder and DHA will be performed separately after the first study. What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals? A research associate has been hired and IRB application was submitted. As soon as IRB application is approved, we will initiate the dietary intervention study. In the mean time we are conducting studies for Specific aim 2: in vitro mechanistic experiments to determine whether and how polyphenols present in bluberries inhibit Toll-like receptor-mediated signaling pathways.
Impacts
What was accomplished under these goals?
Since our AFRI/NIFA project was approved for funding, we have obtained a supplementary funding from the US Highbush Blueberry Council for a study to evaluate the endothelial vasodilator function using the Endo-PAT assay for the subjects consuming the high fat diet supplemted with blueberry powder. We decided also to perform the Endo-Pat assay for the subjects consuming the high fat diet supplemented with docosahexaenoic acid (DHA) supplementation : the additional cost for this assay for the DHA treatment group will be supplemented from our in-house CRIS project funds. The Endo-PAT 2000 is a new approach to assess endothelial vasodilator function in a rapid non-invasive manner. The technique provides values for the calculation of a Reactive Hyperemia Index (RHI), which gives an indication of the endothelial vasodilator function. The RHI is the post-to-pre occlusion PAT signal ratio in the occluded arm, relative to the same ratio in the control arm, and corrected for baseline vascular tone. Studies using the Endo-PAT have shown that the RHI score reflects NO-bioavailability 25. The RHI correlates with the measurement of endothelial vasodilator function with brachial flow-mediated dilatation (FMD). Subjects with a greater degree of cardiovascular disease exhibit a lower score and values are also lower in other conditions associated with impaired endothelial function and risk of cardiovascular disease. Notably, RHI values appear to be predictive of cardiovascular outcomes. A low RHI (indicating endothelial dysfunction) can be reversed with treatment. Therefore, in the propose study, whether blueberry intake improves impairment of postprandial endothelial function will be investigated using the Endo-PAT assay. The IRB committee raised a question about the potential risk of anemia for the study subjects who will visit our Center for four times for different dietary regimens (placebo, blueberry powder, DHA and a combination of blueberry and DHA) and for blood samples to be taken during each visit. Therefore, we decided to perform first a study with three dietary treatments (placebo,blueberry powder and DHA). The dietary treatment with a combination of blueberry powder and DHA will be performed separately after the first study. 3) In the mean time, we have studied whether cyanidin-O-glucoside (one of the major polyphenols present in blueberries) inhibits inflammasome-mediated monocyte activation in monocytes (specific objective 2). 4) A Jr. Specialist (research associate) has been hired to participate in this project. 5) Revised IRB application was submitted to University of California-Davis.
Publications
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