Progress 01/01/21 to 12/31/23
Outputs
Target Audience:The target audience during this reporting period is to students, nutrition professionals, and the public/lay persons. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Due to the interruption of research activities during the COVID pandemic, it was delayed, to some extent, in recruiting and training students as usual. In summary, there are several students supported by and/or involved in by this project partially, including Siauyen Wong (MS, graduated May 2022), Peiran Lu (PhD, graduated in May 2022), MD Salahuddin (postdoc, 10/2022-9/2023) and MD Hasan (PhD student, Jan. 2023-Dec. 2023), and Yashu Tang (PhD student, Jan. 2023-Dec. 2023). One undergraduate (Nathan) completed research lab training/shadowing in summer 2022 How have the results been disseminated to communities of interest?Part studies were shared with kids in the Stillwater Chinese School Summer Camp, entitled Colorful foods and health, June 27, 2022. I also gave talks to multiple institutions in the United States and professional conferences. Dingbo Lin. Carotenoids: More than meet the eye, Department of Nutrition and Food Sciences, Texas Woman's University, April 12, 2024. Invited speaker. Dingbo Lin. Carotenoids: More than meet the eye, Department of Molecular and Structural Biochemistry, North Caroline State University, March 21, 2024. Invited speaker. Dingbo Lin. Carotenoid metabolism in health and disease: A brief update. North America Chinese Association for Nutrition (NACAN) Webinar Series, April 26, 2024. Invited speaker. Dingbo Lin. Food bioactive compounds in prevention of human chronic diseases. The 14th International Conference on Functional Foods. Qingdao, China. March 29-31, 2024. Invited speaker. Dingbo Lin. Carotenoid metabolism: the good, the bad, and the ugly. University of Colorado Anschutz Medical Campus Department of Pediatrics NORC Seminar. October 12, 2023 Dingbo Lin. Dietary carotenoids in energy metabolism and blood glucose control. The 14th Asian Congress of Nutrition. Chengdu, China, September 14-17, 2023 (invited speaker-Alternative ONLINE attendance) Dingbo Lin. Carotenoid metabolism in mitochondrial function and blood glucose control. Department of Biochemistry and Microbiology Seminar, OSU CHS-Tulsa, September 1, 2023 Dingbo Lin. Carotenoid metabolism in glycemic control. Cardiovascular & Metabolic Sciences Seminar Series , Cleveland Clinic Lerner Research Institute, July 21, 2023 Dingbo Lin. Carotenoid metabolism and gut microbiome in obesity and diabetes. The 2nd International INTERACT Symposium on One Health & One Medicine. McKnight Center, Stillwater, OK, July 10-11, 2023 (invited speaker) Dingbo Lin. Dietary carotenoids in immune system function. OSU Honors Symposium on Faculty Research. April 19, 2021 (Zoom, 6:30-7:30 PM) Dingbo Lin. The beauty of carotenoids: from mitochondrial function to innate immunity. University of Colorado Anschutz Medical Campus Department of Pediatrics Nutritional Science Seminar. April 1, 2021 What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
In this project, we treated various mouse models with 50% and 100 % watermelon juice (WJ) in the dark cycle for 4 weeks. All is male mouse strains, including wild type C57BL6J (WT), diabetic db/db homozygous, metabolic dysfunctional beta-carotene oxygenase 2 knockout (BCO2 KO), hyper diabetic db/db/BCO2 double knockout (DKO), and STimulator of Interferon Genes (STING) villi specific knockout mice (STING-VI-KO). Homozygous STIING-VI-KO mice are fertile and do not show any significant metabolic deficiencies, including normal blood glucose levels and blood lipid profiles. We completed mouse phenotyping and microbiome analyses in those mice models and microbiome transplant into germ free mice. The major findings and results are highlighted below: WJ was significantly protective in blood glucose control in all mouse genotypes, though the ranges in blood glucose changes various, suggesting that consumption of WJ would not cause elevation of fasting blood glucose levels in diabetic animals. Histology and related immunohistological assessments results indicated that consumption of WJ was beneficial to intestinal integrity and attenuation of inflammation in diabetic mice. Depletion of BCO2 in BCO2 knockout genotype mice strains (e.g., BCO2 KO and DKO) diminished WJ effects on blood glucose control, to some extent, indicating that disruption of lycopene catabolism by BCO2, one of the WJ bioactive compounds, could eliminate the protective effects and thereby leading to the conclusion that lycopene metabolites can exert predominate roles in those mouse models. There was no significant alteration in glucose control in STIING-VI-KO mice, compared to the WT. In combination with the biochemical findings in STING elevation after WJ in db/db mice, we concluded that the STING response to WJ was secondary, and it was not a causal factor in WJ protection of blood glucose control. Gut microbiome 16S rRNA sequencing and shotgun metagenomics revealed that WJ also shifted numerous changes in gut microbiome profiles in mouse models. We identified three specific microbiome species markers for those mice models, e.g., WJ elevation of the richness of Akkermansia muciniphils and Lactobacillus johnsonili but decreases in richness of Mucispirilum schaedleri and Prevotella sp. PCHR. Those changes in microbiome profiles were aligned with the phenotypes in mice with or without WJ. Gut microbiome transplant results were a mix. We did not see significant blood glucose level changes in those transplanted mice. That suggests the interactions between other gut microbiome members in the community are complex. Future work can be focused on mimicking the interactions in in vitro culture, which would ideally help us tease out or simplify the mechanistic adventure.
Publications
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2023
Citation:
4. Yashu Tang, Peiran Lu, Sanmi Alake, John A Ice, Proapa Islam, Edralin A Lucas, Brenda J Smith, Dingbo Lin. 2023. BCO2 deficiency alters intestinal immunity in mice. OSU Biochemistry Research Symposium, February 2023 (Poster presentation)
- Type:
Journal Articles
Status:
Accepted
Year Published:
2021
Citation:
3. Lei Wu, Peiran Lu, Xin Guo, Kun Song, Yi Lyu, James Bothwell, Jinglong Wu, Olivia Hawkins, Stephen L. Clarke, Edralin A. Lucas, Brenda J. Smith, Winyoo Chowanadisai, Steve Hartson, Jerry Ritchey, Weiqun Wang, Denis Medeiros, Shitao Li, Dingbo Lin. 2021. ?-carotene oxygenase 2 deficiency-triggered mitochondrial oxidative stress promotes inflammation and metabolic disorders. Free Radical Biology Medicine 2021 Feb 20;164:271-284. doi: 10.1016/j.freeradbiomed.2021.01.003
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Progress 01/01/22 to 12/31/22
Outputs
Target Audience:The target audience during this reporting period is to students, nutrition professionals, and the public/lay persons. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Peiran Lu, a PhD student who was partially supported by this grant graduated in May 2022. One undergraduate (Nathan) completed research lab training/shadowing in summer 2022. How have the results been disseminated to communities of interest?Part studies were shared with kids in the Stillwater Chinese School Summer Camp, entitled Colorful foods and health, June 27, 2022. What do you plan to do during the next reporting period to accomplish the goals? Characterize STING-VI-KO mice using high fat diets and watermelon juice treatments in this summer. The expected outcome will be that STING signaling is vital to high fat diets induced hyperglycemia and obesity. We also anticipate that deficiency of STING, to some extent, will abolish watermelon's protective effects in energy metabolism and alteration of gut microbiome in mice.
Impacts
What was accomplished under these goals?
We have generated STimulator of Interferon Genes (STING) villi specific knockout mice (STING-VI-KO). Homozygous STIING-VI-KO mice are fertile and do not show any significant metabolic deficiencies, including normal blood glucose levels and blood lipid profiles. We completed the microbiome analyses in diabetes mice and microbiome transplant into germ free mice and are summarizing the data.
Publications
- Type:
Journal Articles
Status:
Accepted
Year Published:
2023
Citation:
1. Dingbo Lin, Denis M Medeiros. The microbiome as a major function of the gastrointestinal tract and its implication in micronutrient metabolism and chronic diseases. Nutr Res. 2023 (in press). https://doi.org/10.1016/j.nutres.2023.02.007
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2022
Citation:
2. Peiran Lu, Yashu Tang, Kelley Lin, Siau Yen Wong, Jianmin Chai, Paniz Jasbi, Lei Wu, Edralin A Lucas, Hui He, Jiangchao Zhao, Haiwei Gu, Tyrrell Conway, Adrian Wyss, Brenda J Smith, Dingbo Lin. Zeaxanthin-altered gut microbiome is associated with changes in whole body bone mineral density in mice. K-INBRE Genomics Symposium. University of Kansas-Lawrence, May 2022 (oral presentation)
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Progress 01/01/21 to 12/31/21
Outputs
Target Audience:The target audience during this reporting period is to students, nutrition professionals, and the public/lay persons. ? Changes/Problems:Due to COVID associated delay, our request of no-cost extension (1 year) had been approved by NIFA/USDA What opportunities for training and professional development has the project provided?Due to the interruption of research by the COVID pandemic, we did not present data and recruit new undergraduate students as usual. Siauyen Wong and Peiran Lu, both PhD students, had been partially supported by this project. How have the results been disseminated to communities of interest?None. We will have the first manuscript ready for submission for publication this fall. What do you plan to do during the next reporting period to accomplish the goals?We plan to : -complete the collected samples analyses, including metagenomics, metabolomics, and other biochemical assessments. -start breeding of the STING intestinal knockout (iKO) mouse strain. Hopefully, we will also have time to begin the watermelon treatment in those STING iKO mice. -continuously work with Dr. K Kuhn for fecal microbiome transplant -explore the conditions for gut microbiota culture in our anaerobic culture system.
Impacts
What was accomplished under these goals?
We have been successfully generated the animal models of BCO2/db/db systemic double knockout mice (DKO) for both objectives described above. The watermelon juice feeding study in these models have been completed. Samples collected for proposed analyses. We are planning to order STING LoxP mice and villi-Cre mice from Jackson Laboratories to initiate STING villi specific knockout breeding soon (April or May 2022). -generated BCO2/db/db systemic double knockout mice (DKO), and used those mice for watermelon juice study. (BCO2, beta-carotene oxygenase 2; db/db, leptin receptor knockout) -fasting blood glucose and insulin tolerance tests showed that DKO mice are more insulin intolerance compared to BCO2 KO and db/db mice. -watermelon juice (50% and 100 % as replacement of drinking water during the dark cycle) did not increase fasting blood glucose levels in wild type, BCO2 KO, db/db, and DKO mice. Systemic inflammation status will be examined in year 2. -watermelon juice delayed the blood glucose elevation during the development of hyperglycemia in db/db and DKO mice. -intestinal histology assessment had been started. H&E staining slides are ready for microscopy. -decal and fecal samples are ready for gut microbiome metagenomic analyses. -Transplant of Fecal microbiome of DKO mice into germ-free mice has been started in Dr. Kristine Kuhn Lab at the University of Colorado Anschutz Medical Campus. -secured the funds for purchase of the anaerobic culture hood/incubator and iSeq for gut microbiome sequencing (OSU internal funds). -samples collected for gut integrity tests.
Publications
- Type:
Conference Papers and Presentations
Status:
Submitted
Year Published:
2022
Citation:
Presentation to scientific conferences.
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