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National Cancer Institute

Transdisciplinary Research on Energetics and Cancer (TREC) Centers

University of Southern California

Principal Investigator Dr. Michael Goran

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Center Overview

Overall Aim: We seek to establish a transdisciplinary center to address the physiological, metabolic, behavioral, genetic, and environmental influences on obesity, metabolic health, and cancer risk with a focus on minority children. The Center will be directed by two distinguished and internationally known investigators in obesity and cancer research (Michael Goran, Ph.D. and Leslie Bernstein, Ph.D.). Drs. Goran and Bernstein will lead a coherent and synergistic program of three projects, two pilot studies, three research cores, and a training core, each led by collaborative teams of investigators from diverse disciplines.

Projects: In Project 1, we will examine ethnic differences in obesity-related metabolic risk factors for cancer in Hispanic and African American youth and the potential role of strength training as an innovative intervention for improving these risk factors. Project 2 will examine the biological and behavioral bases for the decline in physical activity during puberty in minority girls. Project 3 will examine the "built" environment and urban sprawl as risk factors for the development of obesity in children. The two pilot studies will: 1) develop and pilot test a community-based obesity intervention for Hispanic youth; and 2) examine the contribution of obesity to DNA methylation in the colon. Cores: An Administration Core will provide scientific leadership and oversight, and provide opportunities for new collaboration and dissemination of findings. The research studies will be supported by a Data Management and Analysis Core, and a Human Measures Core. Finally, a Training and Career Development Core will support the next generation of transdisciplinary investigators in obesity and cancer research.

Summary & Significance: We envision this application as an unprecedented opportunity to harness the vast scientific expertise at the University of Southern California. The broad transdisciplinary theme will encompass studies of novel mechanisms that span from the patient bedside to the community curbside, so that more effective interventions in childhood and adolescence can be developed. Our overall vision is based on the concept that preventing obesity and promoting health in children will improve long-term cancer control in the population.

Project 1: Obesity-Related Metabolic Risk for Cancer: Ethnicity and Response to Exercise in Minority Youth
Project Leader: Michael Goran, Ph.D.

Overall Goal: Project 1 will determine ethnic differences in body fat distribution, insulin resistance, insulin-like growth factors and binding proteins, inflammatory markers and oxidative stress in overweight African American and Hispanic children during the critical period of adolescent growth. Thereafter, we will examine the impact of strength training as a therapeutic intervention to improve these risk factors. We build upon previous work to hypothesize that hyperinsulinemia in African American youth is associated with important metabolic differences that could increase long-term cancer risk.

Specific Aims:

  1. To determine the contribution of body fat compartments (visceral fat, muscle fat, and liver fat) and adipokines to insulin resistance in African American and Hispanic youth;
  2. To examine differences in metabolic compensation to insulin resistance between African American and Hispanic youth;
  3. To examine the influence of body fat, insulin resistance, and ethnicity on markers of lipid peroxidation and oxidative stress; and
  4. To determine the effects of a randomized strength training intervention on potential mechanistic factors linking obesity to cancer risk.

Design: Cross-sectional (40 African Americans versus 40 Hispanics) 16-week strength training program in which obese adolescents are randomly assigned to nutrition education or nutrition education plus supervised strength training. Major outcome variables include: insulin sensitivity and insulin response to glucose by intravenous glucose tolerance test; whole body composition (by dual energy X-ray absorptiometry); visceral fat, liver fat, and muscle fat by magnetic resonance spectroscopy; oxidative stress, lipid peroxidation, plasma lipids, and genetic admixture by blood draws; and physical activity by accelerometry.

Significance: Project 1 will shed new light on differences in metabolic risk factors for cancer between African Americans and Hispanics as well as their response to strength training. The contrast between African Americans and Hispanics is of particular interest because while these groups share similar predisposition to obesity, greater insulin resistance, and risk for type 2 diabetes, for the major types of cancer African Americans have substantially greater risk than Hispanics. Furthermore, this study will provide new information regarding the impact of strength training as an anti-obesity and anti-carcinogenic intervention in "at risk" minority adolescents.

Project 2: Insulin Resistance and Declining Physical Activity Levels in African American and Latina Girls
Project Leader: Donna Spruijt-Metz, Ph.D.

Overall Goal: To determine physiological and psychological determinants of the decline in physical activity in Latina and African American girls during puberty. The decline in physical activity that occurs during adolescence has been found consistently across gender, ethnicity, and nationality in human studies, and across species in animal studies, suggesting a biological basis. The pubertal transition in Latina and African American girls represents a "critical period" of development in which increased insulin resistance and decreased physical activity have been noted. These "risky" metabolic and behavioral changes in this susceptible ethnic group may explain, in part, their increased risk for obesity. This pubertal decrease in physical activity also raises future risk of breast, endometrial, and colon cancer.

Specific Aims and Approach: Aim 1 (Longitudinal Study): To determine the direct impact of pubertal insulin resistance in Latina and African American adolescent girls on physical activity, mood, and meanings of physical activity across the pubertal transition from Tanner Stages 1-3. Aim 2: To determine how the impact of puberty-induced insulin resistance on physical activity is mediated by mood and meanings of physical activity. Aim 3: To investigate ethnic differences in the impact of insulin resistance on mood, meanings of physical activity, and physical activity. We will recruit 50 Latina girls and 50 African American girls 9-11 years of age at Tanner Stage 1. Yearly metabolic evaluations and quarterly accelerometry and psychosocial evaluations will be completed for a period of 3 years. A combination of path models and growth curve models will be used to understand the longitudinal impact of pubertal insulin resistance on mood, motivation, and physical activity levels in Latina and African American girls as they mature. Central hypotheses: Pubertal insulin resistance leads to a decline in physical activity. The decline in physical activity in girls is partially biologically programmed, emanating from the "trigger" of insulin resistance, which is linked to affective determinants of physical activity including mood and energy levels, and these metabolic and psychological changes contribute to the marked decline in physical activity that occurs during puberty. This study will be the first to examine the temporal relationship between pubertal insulin resistance and the sharp decline in physical activity experienced by Latina and African American girls during puberty.

Project 3: Influence of Built Environments on the Development of Obesity During Childhood
Project Leader: Michael Jerrett, Ph.D.

Background: Growing evidence now links the built environment to physical activity, dietary quality, and obesity. The goal of this study is to assess the influence of the built environment on longitudinal changes in body mass index (BMI) in a cohort of 11,797 children from 16 communities across Southern California. This study will focus on the contributing role of neighborhood-level factors in the progression toward overweight and obesity or "obesogenic trajectories." We define these trajectories as the temporal progression toward overweight and obesity compared to age-adjusted growth curves for the cohort.

Methods: We build on over 8 yrs of measurements on 6,259 children in the USC Children's Health Study (CHS) (ages 9-10 at enrollment, reaching 18 years at end of follow-up). We will supplement this data set with 4+ years of follow-up on 5,538 children in a new cohort (ages 6-7 years at recruitment with follow-up until they are 11-12 years). Participants have been thoroughly characterized with annual measurements of height and weight, lung function, physical activity, baseline dietary intake, gender, race, ethnicity, and socioeconomic status (SES). CHS data will be integrated with measures of the built environment derived in a Geographic Information System. We will test the impact of the built environment and obesogenic trajectories using spatial statistics and multilevel growth curve models.

Specific Aims: (1) To assess the effects of the neighborhood built environment on obesogenic trajectories; and (2) To explore whether individual variables (i.e., gender, race, SES) and contextual variables (i.e., air pollution) modify the association between the built environment and obesogenic trajectories.

Significance: Specific strengths of this application include the examination of the effects of the built environment on children's prospective change in weight status, direct assessment of children's weight status annually, efficient use of existing environmental and individual data, and the ability to evaluate potential differential effects across ethnicity/race on the relation between built environment and obesity. This project will identify specific variables in the built environment that significantly influence the development of obesity in children. These findings could have public health implications with respect to structuring the built environment to prevent obesity in children.