Source: VIRGINIA POLYTECHNIC INSTITUTE submitted to NRP
DEFINING AMINO ACID METABOLISM IN DISEASE CHALLENGED PIGS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
ACTIVE
Funding Source
Reporting Frequency
Annual
Accession No.
1032219
Grant No.
2024-67012-42410
Cumulative Award Amt.
$225,000.00
Proposal No.
2023-09765
Multistate No.
(N/A)
Project Start Date
Sep 1, 2024
Project End Date
Aug 31, 2026
Grant Year
2024
Program Code
[A1221]- Animal Health and Production and Animal Products: Animal Health and Disease
Recipient Organization
VIRGINIA POLYTECHNIC INSTITUTE
(N/A)
BLACKSBURG,VA 24061
Performing Department
(N/A)
Non Technical Summary
Porcine Respiratory and Reproductive Syndrome Virus (PRRSV) is a debilitating disease that poses both physiological and financial concerns. Low efficacy of current vaccines has shifted the focus from traditional medicine to alternative strategies, such as nutrition, to lessen the impacts of this disease. Traditionally, it was understood that the adverse effects of the illness stemmed from reduced feed intake among affected animals. However, when healthy pigs are fed the same amount of feed as their PRRS-infected counterparts, they exhibit superior growth rates. This suggests that the immune response is consuming vital nutrients present in the diet.To address this issue, intravenous catheters will be placed, and pigs will be given the PRRSV virus. During the challenge, pigs will be given amino acids that are potentially very important for an immune response and growth of the animal. The ability to draw blood easily with little to no stress on the animal allows samples to be collected frequently at different stages of the disease; allowing us to characterize the impact of the disease on different components of the plasma. In addition, we can identify factors that vary based on dietary treatments which will help us identify pathways we can exploit to help mitigate the effects of disease. Our ultimate goal is to modulate the immune response by characterizing metabolic flux and macronutrient consumption of the challenge.
Animal Health Component
20%
Research Effort Categories
Basic
70%
Applied
20%
Developmental
10%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
31135101010100%
Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3510 - Swine, live animal;

Field Of Science
1010 - Nutrition and metabolism;
Goals / Objectives
Given the widespread effects of PRRSV throughout the body and its affect on pigs across various age groups, this presents a unique opportunity to deepen our understanding of the immune system and its intricate interplay with intermediary metabolism. The overarching objective is to delineate between nutrients utilized by the immune system and those directed towards other metabolic pathways. We will achieve the goal through several objectives:1.) identify a feeding strategy to help mitigate weight loss during an immune challenge.2.)determine which amino acids are used by the immune systemandwhich are used for lean tissue accretion during a disease challenge.3.) understand the proliferation and growth of immune system during a challenge.Accomplishing these objectives will not only enhance our ability to classify immune responses but also pave the way for potential modifications to these responses during disease challenges. This knowledge holds promise in identifying pathways that could be harnessed for immune system modulation, potentially expediting the recovery process or reducing the overall morbidity and mortality associated with the disease. The anticipated outcome of this project includes the development of amino acid requirements tailored to different stages of disease challenges. This will shed light on the specific amino acids utilized at various points during the challenge. Ultimately, this endeavor aims to deliver tangible benefits to the swine industry while deepening our comprehension of the immune system and its reliance on macronutrients for optimal function.
Project Methods
Efforts: Scientific studies related to this project will be completed in a BSLII facility to ensure containment of the pathogen. Animals will be housed individually to account for feed intake and to ensure longevity ofsurgically placed catheters. Samples will be collected throughout a PRRSV challenge to evaluate metabolism and circulating amino acids. Efforts will be focused on making presentations and peer-reviewed journal articles that will help explain and disseminate information in a coordinated manner. Results will also be arranged so they can be worked into an undergraduate nutrition class.Evaluation: Rigor and reproducibility will be a focus of this project. To ensure both, weekly meetings with mentors will be held to discuss ideas and progression of results. This will not only ensure that questions are answered appropriately and thoroughly but that the correct questions are being asked. Discussed in these meetings will be topics for future studies, mechanisms that need further delineation,and application of all work to the swine industry. Data collected will be analyzed via statistical software SAS. Analyzed data will be discussed with project personnel, collaborating scientists, and industry professionals to best interpret results from our studies.

Progress 09/01/24 to 08/31/25

Outputs
Target Audience:During this reporting period, the project successfully engaged multiple target audiences across academic, industry, and institutional sectors. Notably, this semester marked the inaugural offering of the Introduction to Animal Health course, designed for upper-level undergraduates. Approximately 25 junior- and senior-level students attended regularly. The course was tailored for students preparing for professional or graduate programs and emphasized high-level concepts in animal health. The scientific community and industry professionals were also key audiences. Finally, a substantial audience was reached within Virginia Tech and the College of Agriculture and Life Sciences, including undergraduates, graduate and professional students, and principal investigators. This diverse academic community continues to serve as an important base for disseminating research findings and fostering interdisciplinary collaboration. Changes/Problems:My plan was to present this past year in Chicago at CRWAD however, due to weather and travel arrangements, I was unable to attend so I will attend another conference this next reporting cycle. For the second part of the project, we are choosing to foucs on lipid supplementation in rations instead of branched chain amino acids because data from this current study suggest this situation may be more fruitful. However, as mentioned this study is on the ground running and the pigs are doing very well. This will not change the overall goal of the project and should even help the study bring positive data to the industry. What opportunities for training and professional development has the project provided?I have had several excellent opportunities to learn and grow in my education and skills to become a tenure-track faculty member. First, I was able to have a consistent role in the classroom giving lectures and designing projects for students. Interaction with this group of individuals was fantastic and I learned several teaching skills/philosophies from this activity. Further, I learned about the time commitment that is required to handle a 3 credit hour class. While not a majority of my time by any means, it was definitely not an insignificant amount of time to prepare, lecture, and grade tests. Learning experiences on the research side have been just as, if not more, fruitful than the teaching experience. My time in Dr. Najt's nutritional biochemistry labratory has culminated in learning several new techniques for isolating, processing, and testing mitochondria from several different fractions within the cell. Not only will this work be extremely useful in my future career, it is translating to publications in an area I had no formal training on (healthy aging) until my postdoctoral position started. Live tissue assays such as respirometry, hepatic perfusions, and fatty acid labelling have been central to my training in the Najt Laboratory. I have also learned several wet lab techniques that will give me a competitive edge for building programs such as proteomic and lipidomic data cultivation and analysis. Working with stable isotope tracers in vivo (a large component of this project) has allowed me to hone my skills as well as study a whole new area of intermediary metabolism for me, mainly amino acids. This fellowship has afforded me several opportunities thus far and there are many more to come during the second half of the project. How have the results been disseminated to communities of interest?Once data from this study is in publishable form, abstracts will be sent to CRWAD and Animal Science. Currently, this data has been presented in several lab meetings and departmental seminars for feedback and additional measurement suggestions. These results have also been discussed with mentors and collaborators from other universities for alternative viewpoints. The second year of this fellowship is expected to have several first-author publications and abstracts of outlined research projects. The first reporting period was used largely to complete animal and labwork, which was accomplished, and begin writing manuscripts. We are well on track to meet all expected goals set previously. What do you plan to do during the next reporting period to accomplish the goals?Several of the reported milestones from this study have been completed. There is one measurement left that will make up it's own figure then all the data is collected for this project. In addition, live animal work on the next step of this project, feed interventions, is already over halfway through (Goal 1). The second study labwork is more straightforward as a large proportion will be growth and ex vivo measurment data. In order to complete these studies, I will be completely finished with labwork from both studies by November of this year (Goal 2). This is perfect timing for the two conferences I plan to present in January and March. Following wetlab work, data analysis and manuscript preparation will following with an intent to publish early in 2026. Following the publication of these 2 manuscripts, I will began to move toward writing a review article in the area in which these studies belong (Goal 3). Given the successful first half of this project, the second half will be very prolific and rewarding. In addition to tangible milestones that were set at the beginning of this finding period, this fellowship has provided exceptional preliminary data that will kick-start a successful program in swine health and nutrition. These future study ideas are perhaps more valuable at this point in a young career than the publications that will result from this work. This is obviously a huge statement as papers and productivity are essential during this part of my career

Impacts
What was accomplished under these goals? The live animal and viral components of this study have been completed. This has resulted in several organs being harvested for analysis. All viseral organs and several individual muscles were collected from this study. A significant proportion of the data has been collected, analyzed and made into figures. We have begun to highlight some of the key metabolic pathways that are altered during a disease challenge apart from lack of feed intake in pigs. In doing so, we are able to take aim at specific amino acids to be used for supplementation in rations. To determine which amino acids are limited for optimal lean tissue accretion, we first need to determine what is not being used for lean tissue accretion in the body. These questions can be answered with samples or data that has already been collected. Further, we need to push into exploration of fatty acids as constructive feed additives to swine diets during a challenge. This will be the second half of this project. However, there is signifciant progress that has been made with this project to the point where it could be published as is. There are still two measurements I would like to complete in all tissues to make this project as impactful as possible. All the tissues have already been ground for this analysis. We are simply waiting for the GCMS to be open to run these samples.

Publications

  • Type: Theses/Dissertations Status: Accepted Year Published: 2024 Citation: Hepatic lipid metabolism in neonatal pigs