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COMPREHENSIVE TISSUE COLLECTION FROM HIGH AND LOW FEED EFFICIENT COWS: ELUCIDATING TISSUE METABOLISM AND FETAL PROGRAMMING OF COW AND FETUS

Objective

Experiments designed to answer the most pressing scientific questions must balance scientific appropriateness, ethicality, feasibility, and expense. As a result, we often face limitations to breadth or depth of analysis, studies are frequently underpowered, or we must use proxy measures or tissue subsamples. Rarely do we have the opportunity to access sufficient samples (quantity and replication) to allow us to address critical gaps in our understanding of nutrient use efficiency in dairy cattle that would otherwise be not only cost prohibitive, but ethically prohibitive. This proposal focuses on leveraging a unique, once-in-a-career opportunity, closure of a research dairy, to conduct a thorough examination of tissue-level metabolism in phenotypically characterized cows through an unfortunate but necessary culling of 80 dairy cows from the USDA Beltsville Agricultural Research Center (BARC) dairy and is being overseen by researchers of the Animal Genomics and Improvement Laboratory (AGIL). This situation provides a once-in-a-career opportunity for scientists to partner together to fully examine every tissue in phenotypically characterized dairy cows and their developing fetus in a comprehensive ethical manner to answer questions about whole-body nutrient use efficiency and coordination to yield a range of feed efficiency (FE) metrics and methane emissions. This affords us the ability to conduct an extensive tissue collection from 50 of the cows selected (highest and lowest FE) for scientists from USDA AGIL and the University of Wisconsin-Madison to partner and address a range of research questions. Collection of maternal and fetal tissues to this extent has rarely been done [1], and the animal expense alone would preclude the objectives presented herein from being completed without this timely collaboration. Slaughter of cows will begin in August 2023 and continue for 18 months. Dr. Ransom Baldwin, VI and colleagues at USDA AGIL will be addressing the role of gastrointestinal and service tissues as a component of energetic efficiency and how growth and differentiation of these tissues is regulated at the genomic level. USDA AGIL funds are available to address gastrointestinal objectives and to collect additional tissues. With this proposal, we are seeking funds to analyze the additionally collected tissues to answer novel objectives that would not be possible without additional funding. Given the lifespan of the tissues for the desired analysis, this proposal is unique, collaborative, and of a time-sensitive nature. The proposed objectives here will be executed in conjunction with serial slaughter of cows at the USDA BARC facility, and the research questions being answered herein are unique to those being addressed by AGIL research scientists and represent an attempt to maximize knowledge gained.Our long-term goal is to understand nutrient use efficiency at the tissue and whole-animal level to improve FE and reduce methane emissions in dairy cows. Although aspects of this are being examined, to date a comprehensive examination of whole-body influences on FE and methane emissions has not been conducted; thus, this situation presents an opportunity to fill a critical gap that is typically unattainable due to costs associated with slaughtering and collecting multiple tissues from multiparous lactating dairy cows of divergent FE. The objectives in this proposal will allow us to examine the contribution of the liver, muscle, adipose, and lymph nodes to multi-lactation, whole-animal FE and methane emissions phenotypes in conjunction with complimentary examination of gut physiology and microbiome analysis by USDA AGIL collaborators. Additionally, a subset of cows will be pregnant at the time of slaughter (150 days in milk, DIM), allowing us to examine the role of maternal FE on fetal tissue development. The central hypothesis of this proposal is that tissue efficiency and nutrient use influences whole-body FE and methane emissions, and that maternal FE status influences nutrient availability to, and programming of, tissues in the developing fetus.To test this, we propose three Specific Aims:Specific Aim #1: Determine if shifts in nutrient metabolism are coordinated across tissues to contribute to whole-body FE. Based on our current data, we hypothesize that gene expression and protein abundance related to fatty acid and amino acid oxidation and immune response in liver, muscle, adipose, and lymph nodes contribute to FE divergence and individual animal variance.Specific Aim #2: Evaluate the fatty acid composition and relative metabolic activity of adipose tissue depots. Of fatty acids that differ between cows of divergent FE, some are likely mobilized from internal adipose depots, consistent with varying metabolic activity of different adipose depots. We will determine if internal adipose tissue depots contribute to high vs. low FE.Specific Aim #3: Examine if the genomic and metabolic differences that lead to high vs. low FE influence fetal development. In utero exposure to nutrients presents a powerful mechanism to impact offspring growth rate and body composition from birth to maturity. We will determine the influence of maternal FE status on fetal weight and pathway regulation.

Investigators
WHITE, H.; Baldwin, RA, L..
Institution
UNIV OF WISCONSIN
Start date
2024
End date
2028
Project number
WIS06004
Accession number
1032072