The overall objective of ttie UCSD TREC Center is to assemble transdisciplinary scientific collaborators to address questions regarding insulin resistance and inflammation underlying the association of energetics with breast cancer carcinogenesis, from the celi to the community. In Project 1, we will use obese mouse models to investigate whether the beneficial anti-inflammatory and insulin-sensitizing effects of u)3 fatty acids will reduce breast tumor growth and metastasis and whether the w3 fatty acid receptor GPR120 is the critical mediator of those cancer-protective effects. In Project 2, we will conduct a triai in obese women to examine differential response (depending on insuiin resistance status) to dietary macronutrient composition. Outcomes will include weight loss, hormonal factors, and markers of inflammation as well as nutrient-gene interactions associated with polymorphisms in IL-6 and TNF-a genes. Project 3 will investigate the degree to which metformin, a lifestyle intervention, or both, can reduce breast cancer mortality among ovenweight/obese, postmenopausal breast cancer survivors. We will use an innovative Biomarker Bridge design that links clinical outcomes from a breast cancer survivor cohort with intermediate outcomes from a randomized controlled trial. Project 4 will advance the science of energy expenditure estimation by using branched equation modeling techniques and artificial neural networks to analyze accelerometer and heart rate data from participants in Projects 2 and 3. Global Positioning System data, which track individuals' spatial-temporal paths, combined with existing Geographic Information Systems data for San Diego County, will allow us to develop obesogenic environmental exposure estimates and relate these to metabolic risk factors. Dr. Patterson, the PI forthis proposed Center, has considerable research experience in nutrition and breast cancer prevention and a strong background in leadership and management in academia and industry. The central leadership entity ofthe UCSD TREC Center will be the Executive Scientific Committee, composed of Project and Core leaders. This Committee, assisted by the Administrative Core, will provide scientific and operational oversight of the Shared Resources (Biostatistics &Bioinformatics and Biorepository) as well as the transdisciplinary Training Program and the Developmental and cross-TREC Pilot Project Core. We believe that the TREC Center proposed herein has the potential to make significant contributions to understanding the link between obesity and breast cancer and provide insight regarding interventions with broad population impact for prevention and control of disease.

Public Health Relevance

The overall objective of the UCSD TREC Center is to enhance knowledge regarding insulin resistance and inflammation underlying the association of energetics with breast cancer carcinogenesis. We wiil meet this objective by implementing 4 transdisciplinary and interrelated research projects, 2 shared resources and training and pilot project cores. An Executive Scientific Committee, supported by the Administrative Core, will be accountable for all components ofthe TREC Center.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
3U54CA155435-03S1
Application #
8688944
Study Section
Special Emphasis Panel (ZCA1-SRLB-4)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
Total Cost
$40,579
Indirect Cost
$14,399
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Kerr, Jacqueline; Patterson, Ruth E; Ellis, Katherine et al. (2016) Objective Assessment of Physical Activity: Classifiers for Public Health. Med Sci Sports Exerc 48:951-7
Le, Tran; Flatt, Shirley W; Natarajan, Loki et al. (2016) Effects of Diet Composition and Insulin Resistance Status on Plasma Lipid Levels in a Weight Loss Intervention in Women. J Am Heart Assoc 5:
James, Peter; Jankowska, Marta; Marx, Christine et al. (2016) ""Spatial Energetics"": Integrating Data From GPS, Accelerometry, and GIS to Address Obesity and Inactivity. Am J Prev Med 51:792-800
Fernandez, Marina O; Sharma, Shweta; Kim, Sun et al. (2016) Obese neuronal PPARγ knock-out mice are leptin sensitive but show impaired glucose tolerance and fertility. Endocrinology :en20161818
Marinac, Catherine R; Nelson, Sandahl H; Breen, Caitlin I et al. (2016) Prolonged Nightly Fasting and Breast Cancer Prognosis. JAMA Oncol 2:1049-55
Schmitz, Kathryn H; Gehlert, Sarah; Patterson, Ruth E et al. (2016) TREC to WHERE? Transdisciplinary Research on Energetics and Cancer. Clin Cancer Res 22:1565-71
Chung, Heekyung; Chou, Winjet; Sears, Dorothy D et al. (2016) Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity. Metabolism 65:1743-1754
Patterson, Ruth E; Marinac, Catherine R; Natarajan, Loki et al. (2016) Recruitment strategies, design, and participant characteristics in a trial of weight-loss and metformin in breast cancer survivors. Contemp Clin Trials 47:64-71
Mitchell, Jonathan A; Godbole, Suneeta; Moran, Kevin et al. (2016) No Evidence of Reciprocal Associations between Daily Sleep and Physical Activity. Med Sci Sports Exerc 48:1950-6
Cho, Chang Gun; Pak, Kwang; Webster, Nicholas et al. (2016) Both canonical and non-canonical NF-κB activation contribute to the proliferative response of the middle ear mucosa during bacterial infection. Innate Immun :

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