Duration: 10/01/2014 to 09/30/2019

Administrative Advisor(s):

NIFA Reps:

Non-Technical Summary

Statement of Issues and Justification

NCCC210, Regulation of Adipose Tissue Growth in Meat Animals, meets the needs of several stakeholder communities, namely, consumers, livestock producers, and scientists. The committee is composed of scientists with broad interests and expertise in factors that affect the development and composition of adipose tissue in meat that is an important component of human diets. The need to control excessive adipose tissue growth, to identify the fatty acid composition of this tissue, and understand the underpinnings of lipid metabolism in adipose and muscle will provide consumers with meat and meat products with enhanced nutritional value. Meat animal producers will have greater information to make informed decisions about production practices that will enhance meat animal productive efficiency, sensory characteristics, and advance nutritional contributions of meat in human diets. Most importantly, scientists will benefit from data exchange, developments in techniques and methodology that arise from the project through advancing the quest for knowledge of adipose tissue biology. Indeed, adipose tissue presents a dynamic metabolic paradigm as knowledge of its composition, biochemistry, molecular biology, endocrinology, and morphology rapidly progresses. Importance of the work The Project Committee meets annually to report and discuss research conducted by individual members, and to advance collaborations among members. The importance of the work conducted by the Project members in the context of the annual meeting and year-round regular correspondence is best summed up as development of ideas and strategies, and critique of planned studies, so that subsequent research is conducted to provide data of importance to advancement of adipose tissue biology of meat animals. In the light of exploding understanding of adipose biology there is a critical need to further continue this research with meat animal species and comparative animal models. If the research of this Project is not conducted, or if the group does not meet to advance the research, then knowledge and understanding of current research technologies will be stifled through the void in scientific interchange. The centrality of adipose tissues in whole body metabolism puts this Committee's expertise and work at the epicenter of meat animal lipid research. Continuing this project group will result in further enhancement of biological understanding that is relevant to meat production strategy, dietary qualities of meat products for use in human diets. Because the project's science focuses in part in energy partitioning and lipid trafficking, it has implications for milk production and quality, as well. In addition to clear agricultural relevance, the project members' efforts in elucidating adipose biology and fat metabolism also contribute to knowledge important to public health, e.g. obesity and related metabolic maladies. NCCC210 and its predecessors have been at the forefront of animal fat synthesis and deposition related research for well over 60 years. Initially the committee had a strong meat science orientation which over the years expanded also into areas of growth and development, nutrition and the biology of obesity. While adipose tissue is necessary for survival to supply and store energy and as an endocrine organ, excess fat is expensive to produce and is unwanted by consumers of lean meat. However, the deposition of intramuscular (marbling) adipose tissue must be promoted to achieve maximum carcass/product quality (for the producer) as well as often times a desired eating experience (for consumers). Animal growth can be modified to decrease fat production by nutritional, pharmacological, and physiological control of intrinsic or extrinsic processes, but this must be balanced with maintaining marbling deposition. Project Committee members continue to be the primary multi-state and Land Grant Universities contributors in the area of adipose tissue biology. Over the last 40+ years the committee has been closely aligned with NC1184 (a national scope multi-state committee) which was organized to concentrate on meat animal protein metabolism and muscle biology. Predecessors of NCCC210 were initially a major contributor to solving the then critical issues in meat animal fat metabolism including such topics as soft pork. Committee members were also keenly interested in comparative lipid metabolism and were among the first to establish the sites and mechanisms of de novo fatty acid synthesis across different species. Aside from many peer-reviewed publications in animal fat biology, a landmark publication at the time was Biology of Fat in Meat Animals, published by the Project Committee members in 1976 (College of Agriculture, University of Wisconsin). Members have and continue to focus on nutritional/ pharmacological treatments to change food animals to a more lean body composition. The utility of dietary conjugated linoleic acids in regulating fat deposition and the potential use of thiazolidinediones (human diabetes medicine) in marbling has been pursued more recently. Over the last 30 years mechanisms controlling adipocyte hyperplasia, differentiation, and growth (hypertrophy) and effects of somatotropin and beta-adrenergic agonists on body composition were also emphasized. An important outcome of the latter research was publication of The Biology of Fat in Meat Animals: Current Advances, by Project Committee members in 1995 (ASAS Press). Committee members also spawned the emergence of growth biology in University (Animal Sciences) curricula and in the establishment of the Growth and Biology section in the Journal of Animal Science. The present scope of NCCC210 (NCR 97) Project Committee members is national and includes academic and USDA/ARS participants from throughout the USA. The impact of NCCC210 is not only felt in U.S. academia and government laboratories, but also in the food production and harvesting sector both in the U.S. and on the international stage. Different industry representatives, keynote speakers, and ad hoc participants are invited to each meeting to provide a unique perspective on adipose tissue biology that complements Committee member expertise. As an example, Dr. Shih-Torng Ding, National Taiwan University Professor and former postdoctoral research associate of Dr. Harry Mersmann (retired NCCC-097/210 member), continues to provide the committee with an international perspective through his guest participation. Dr. Sean Adams (USDA Western Human Nutrition Research Center), Research Leader for the Obesity and Metabolism Research Unit, helps link Committee findings and expertise to nutrition and human metabolic health application. Currently, NCCC210 members address problems in adipose tissue biology by using techniques in molecular biology/gene expression, metabolite and fatty acid quantification and immunology. One continuing theme in the committee efforts has been to develop, perfect and utilize cutting-edge experimental systems to address contemporary issues in what is now often referred to as lipidology. Thus, members are now planning to adopt high-throughput procedures in metabolomics, gene expression, micro-array analyses, new PCR technologies, next generation sequencing (DNA) and RNA sequencing. Developing broad use of these methods for meat animal lipid metabolism and associated areas as obesity by a group of lipid experts on the technical committee from various institutions (bio-medicine and agriculture) will assure (and has) adoption of such experimental approaches by colleagues working in growth and development, fat metabolism, meat sciences and nutrition at various land-grant institutions. Due to the species-independent nature of modern omics research analytical tools, the Committee has a unique opportunity to leverage these approaches to push the field of meat animal metabolism to new heights. Before about 1990, basic mechanisms of fat synthesis and oxidation were typically studied using key enzymes in fat-related metabolic pathways. In the biomedical community, similar such work was proceeding, as well as early development of adipocyte tissue culture. A major impetus into studying molecular regulation of adipocyte differentiation and lipid metabolism in food animal species was the work of Goldstein and Brown (1) and Spiegelman (2). They discovered and delineated the roles of specific transcription factors in molecular regulation of de novo lipogenesis and cholesterol metabolism. Emergence of these hitherto unknown new paradigms in molecular regulation of cell differentiation and fat metabolism gave great impetus to similar studies with food animal species by NCCC210 committee members at participating state institutions and USDA laboratories as well as the biomedical community at large. Earlier studies by NCCC210 participants have now been extended to studies of gene expression and genomic approaches to even further delineate the intricacies of molecular regulation of lipid metabolism and energy balance. For example, utilizing microarray and RNA sequence analysis and targeted gene expression facilitated by laser capture micro-dissection and real-time PCR on serial tissue samples from cattle and pigs, workers at the Alabama Station (Bergen, Brandebourg: Auburn Univ.) are obtaining new data on potential physiological factors related to residual feed intake/feed efficiency, heat tolerance and the molecular regulation of adipose depot development as related to marbling. Other participating stations have also utilized these approaches to study the role of genetics/genomics in fatty acid composition in beef cattle (Beitz: Iowa State Univ.), and other transcription factors and gene cascades (Lee: Ohio State Univ.) as well as micro-array based gene profiling of either fasted or insulin-deprived chicken (Voy, Univ. of Tennessee) and pig (Hausman: Univ. of Georgia) adipose tissues. Research by various members of the Committee is also proceeding to identify additional transcription factors critical in regulating proliferation and differentiation of adipocytes. Among these are zinc-finger protein transcription factors which play a pivotal role in adipocyte differentiation (Du: Washington State Univ.). While most of the Committee members have continued to focus on farm animal systems in their research, present efforts in molecular regulation of adipocyte differentiation and overall molecular regulation of fat metabolism is closely aligned with work done principally with laboratory rodents and transformed fat cells in culture. This clearly denotes that the committee membership and ad hoc participants are involved in cutting-edge research in lipid metabolism principally oriented toward animals for food use. Not all research by the committee over the last 10 years is solely focused on gene-level regulation of lipid metabolism. Several project committee members have studied mechanisms for conjugated linoleic acid modification of growth and fat deposition (Barnes: W. Virginia Univ.), while another member studies development of omega-3 fatty acids in adipocytes of grass-fed beef. Stearoyl CoA desaturase (SCD) has a significant role in lipid metabolism in humans and food animals. It is a key enzyme that imparts some softness in animal fats by converting stearic acid to the monounsaturated oleic acid (18:1, n9) and SCD is transcriptionally controlled. Other research has focused on how to increase understanding of the role of the extracelluar matrix and dietary fatty acids on regulation of inflamation in adipocytes (Ajuwon: Purdue). The role of fatty acid oxidation in neonatal piglet survival and postnatal growth continues is a principal area of study by the North Carolina Station (Odle: NC State Univ.). Finally, there have been studies among several stations exploring the role and benefits of omega 3 highly unsaturated fatty acids (HUFA) primarily in rodent or swine lipid metabolism. While important for many aspects in meat production, such findings also are useful as animal model studies to human nutrition and medicine. Application of metabolomics approaches to questions of fuel trafficking and obesity-associated phenotypes has been a focus of some Committee member efforts (Adams: USDA WHNRC, Davis). These studies have, for instance, highlighted interactions between perturbations in branched chain amino acid metabolism, changes in fat oxidation and metabolic disease outcomes (3, 4). This may be applicable to animal food production in light of leucine's known role in triggering protein synthesis, since a goal of meat production is to obtain desired lean/fat ratios and fatty acid ratios (omega 3/omega 6). These efforts are an example of significant interactions between the technical committee and human nutrition and lipid metabolism scientists elsewhere and indicate a working relationship between NCCC210 and scientists in related areas of biomedicine and human nutrition. In the last few years there has been increasing interest in utilizing stromal vascular cells (pre-lipid) and dedifferentiated fat cells as a source of stem cells for research and therapeutic purposes. This is a novel extension of the plethora of work with cell cultures with primary fat cells or specific cell lines. Dr. Shih-Torng Ding of the National University at Taiwan (an international ad hoc regular participant in NCCC210) has made some interesting advances here while committee associated scientists at Washington State, Georgia and Auburn have recognized the possibilities of stem cell production from adipose cells and have written a timely review paper (5). Further the deliverables from the committee include extensive explorations of comparative lipid metabolism and application of data to human nutrition and lipid metabolism issues. Another influence of the Committee on agricultural and life sciences research has through timely publications and books. During the 2004-2009 project period, nine members of the Committee published a paper entitled The Biology and Regulation of Preadipocytes and Adipocytes in Meat Animals (6). This paper is now among highly cited articles in the Journal of Animal Science. More recently, based on their wide experience in lipid metabolism and nutrition, Committee members from Washington State University, University of Georgia and Auburn University have published a paper entitled A long journey to effective obesity treatments: Is there light at the end of the tunnel? (7). Committee members were invited to speak at a 2011 joint conference (Agri-Medical Research: Providing Dual Benefit for Agriculture and Human Health) sponsored by American Society for Nutrition (ASN), American Society of Animal Science (ASAS), and American Dairy Science Association (ADSA) in New Orleans. Committee members initiated a NCCC210-sponsored American Society for Nutrition symposium entitled Adipose and Lipid Biology: Crossing Taxonomic Boundaries for which speakers submitted follow-up articles to the journal Advances in Nutrition (8). Thus, the Committee has remained very active in knowledge dissemination to the animal science and nutrition communities through publication and conference participation. Members have hundreds of thousands of dollars in grants each year from USDA/AFRI, commodity groups, industry, and state funds. They serve on multiple journal editorial boards (J. Anim. Sci., J. Nutr., Dom. Anim. Endocrin., Exp. Biol. Med., Adv. Nutr.), serve as Editor and section editors for J. Anim. Sci., review multiple grants, present numerous seminars and symposium talks, and organize and chair meeting sessions and symposia. Technical feasibility of the plans and research The research of Committee individuals is greatly enhanced because of the interaction at the meeting with detailed discussion, critique and trouble-shooting of experimental design, methods, results and interpretation. Members with less expertise in a specific area or sub-discipline have access to input by other members with demonstrated expertise. Thus, detailed presentation and discussion of research design, methodologies and results at the meeting greatly increases the feasibility of the projects and the probability of success. As research approaches and methodologies continue to advance and evolve, Program Committee member contributions are markedly improved because of these interactions. Advantages of doing the work as a multi-state effort Advantages of collaboration as a multi-state effort are best defined as diversity of efforts emphasized by members from the individual states. The diversity includes species, discipline, and technical emphasis. This allows the Committee to span needs of consumers and industry more completely and to leverage the most precise and advanced technologies. Species diversity is partially dictated by inventories of these food producing animals in specific regions of the country. For example, faculty at the University of Wyoming focus on sheep and cattle, those in Texas and University of California-Davis focus primarily on beef cattle, and faculty working with swine are represented by a large number of Committee members. Moreover, other members of the Committee emphasize cell and tissue culture to accomplish goals consistent with those of the NCCC210 project. Likely impacts of successful collaboration Outcomes of collaboration among Project Committee members are not limited to the confines of the annual meeting. Individuals and collaborators who are a part of this Project Committee have been and continue to be successful in obtaining extramural research grants because of the research conducted, in part, in conjunction with input and involvement of Project Committee members. The Project Committee members continue to conduct symposia focusing specifically on regulation of adipose tissue accretion in food producing animals at national scientific meetings, as well as publishing proceedings and books on this topic. Advancements realized by Project Committee members also positively impact the biomedical community because of the direct link to human nutrition and human adipose tissue biology that has relevance to disease states such as obesity, inflammation, and the metabolic syndrome. The greatest impacts of the NCCC210 multi-state project have been: 1) Enhanced quality of research in making the whole greater than the sum of the parts through collegial collaborations, particularly at the annual meeting that is held preceding the Experimental Biology meetings; 2) The broad utilization of the knowledge base that is communicated through Project Committee member publications that result under the auspices of the NCCC210 Multistate Project Committee; and 3) Future agricultural science leadership development; the NCC210 Project Committee meeting always includes participation and speaking opportunities for graduate students and postdoctoral fellows, and an unparalleled networking opportunity. Several Committee Members were previous students and postdoctoral associates who now lead academic and government laboratory groups.

Objectives

Procedures and Activities

NCCCC210's renewal will continue to provide expertise and national leadership for research in modern concepts of adipocyte biology, in vivo fat deposition, intramuscular/intra-fascicular adipose development and animal growth. This is expressed in the contribution of member's expertise to review panels such as USDA NRI Animal Growth and Nutrient Utilization grant programs. In addition members have been on the joint NIH/USDA panel on agricultural animal research as a research model for biomedical issues. A significant crossover from animal to human lipidology research will be a main theme of the committee's activities in this renewal period (2014-2019). While adoption of new experimental strategies and equipment has been a hallmark of this committee, the areas of comprehensive lipidomics, high throughput gene expression based on RNA sequencing and utilization of bioinformatics in our research will be much more evident during this renewal period. This will allow the committee to focus on within species lipidology for specific understanding in enhanced detail and through the use of bioinformatics will enhance the impact of comparative lipidology. Share and summarize preliminary data from various stations to develop multi-institutional grants in adipocyte biology. An emerging area here is the use of adipose tissues for stem cell production. In addition develop avenues to share unique infrastructures/equipment from different representative institution. Such may include advanced ultra-sensitive chromatography equipment for lipid metabolomics, mass spectrometer and sequencing /bioinformatics technology not available to all committee members. Plan two symposia programs to be held at annual meetings of Experimental Biology (EB/ASN) and American Society of Animal Sciences (ASAS). This will include identifying timely topics and speakers. As indicated in objective 3, the plan is to utilize the extensive expertise of committee members. The EB symposia will be targeted toward comparative lipid biology and adipocyte cell function. For ASAS the symposium will be targeted to food animal lipidology, myocyte-adipocyte cross talk and regulation of adipocyte differentiation. In addition the committee desires to write additional review articles for major publications emphasizing lipid biology and obesity and role of climate change on adipose deposition and animal growth (see objective 3). Within the committee membership, adipocyte culture and differentiation mechanisms remain key components of their research. This research is likely to be expanded to attempts to systemize production of stem cells from adipose tissues. The committee will maintain its influence by continuing interactions with other scientists in the lipid metabolism area in the meat sciences, nutrition and biochemistry communities by active participation in activities of these groups and learned societies. Above all however the principal activities of the committee will revolve around the annual meetings.

Expected Outcomes and Impacts

Projected Participation

View Appendix E: Participation

Educational Plan

The annual Project Committee meeting is enhanced by attendance of graduate students and postdoctoral fellows associated with members of the Committee. The gathering is very informal around a large table. These young scientists are encouraged to actively participate and to present results to the group and several have been employed to tenure track positions and now contribute as state representative Project Committee members. Typically, a representative from industry is invited to participate/present at the meeting allowing members to make contacts and discuss funding opportunities. New members are solicited, as current members become aware of scientists doing research on adipose tissue growth. The results from the research of Project Committee members are disseminated in a multiplicity of reviewed journal articles coupled with numerous published symposia proceedings and book chapters.

Organization/Governance

The Governance for NCCC210 includes the election of a Chair, a Chair-elect, and Secretary. All officers are elected for one year. The Chair-elect arranges the meeting for the subsequent year. The annual meeting is held in junction with Experimental Biology (Federation of American Societies of Experimental Biology). Continuity is provided by the stable membership and excellent attendance. Administrative guidance is provided by an assigned Administrative Advisor and a CSREES Representative.

Literature Cited

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Land Grant Participating States/Institutions

AL, GA, HI, IA, IN, MS, NC, OH, TN, TX, VT, WA, WV, WY

Non Land Grant Participating States/Institutions

University of Arkansas, University of Arkansas for Medical Sciences, University of Missouri - Columbia