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The Relationship of Leptin and Stress Among Worksite Employees Rachel M. Ceballos April 20, 2007 I. Background: Leptin ■ Hormone – Released: adipocytes, ovaries, mammary glands ■ Receptors – Distributed: throughout the body (central/peripheral) ■ Function: – Leptin can contribute to the regulation of… -Metabolism -Puberty -Hematopoiesis -Immune Function -Stress Systems I. Background: Leptin & Stress ■ What is the relevance to cancer prevention and control? Stress - - Immune Function (e.g. TH1) + Leptin Cancer I. Background: Leptin and Stress Animal Model ■Lower leptin levels – Wistar Male and Sprague-Dawley Male and Female rats – Immobilization Stress: 3 hrs/day for 3-10 days or 20 min/day for 21 days (Harris et al., 2002; Makino et al., 1999: Gomez, Houshyar, & Dallman, 2002;Ceballos et al, 2006) ■Higher leptin levels – Long Evans Male and Female rats – Immobilization Stress: 20 min/day for 21 days (Ceballos, Faraday & Klein, 2006) I. Background: Leptin and Stress Human Model Lower leptin levels – Female medical students – Post-menopausal women exposed to acute laboratory stressor – Healthy adults following physical activity (Al-Ayadhi, et al, 2005; Ceballos,et al, in preparation; Legakis et al, 2004) No difference – Healthy men and pre-menopausal women exposed to acute laboratory stressor (Ceballos, et al, in preparation) ■ High Leptin Levels – Male Japanese government employees (Otsuka, et al, 2006) I. Background: Purpose Pilot Study to examine the relationship between leptin and stress in a community based sample II. Methods Randomized Trial: Promoting Activity and Changes In Eating, PACE (Beresford, S.A.A., P.I.) ■ 30 Worksites in the Seattle area – Worksites with 40 and 350 employees – Pair-matched on several characteristics (e.g., size, % women, baseline response rate) – Worksites randomly assigned to intervention or comparison (delayed intervention) arm – Subgroup of individuals asked to provide blood sample and complete additional questionnaires II. Methods ■ Participants – 10 worksites – N=80 • 33 Men, 47 Women • Mean Age: 41.62 (11.13) • Education: Some high School High School Graduate/GED Technical/Business School Some college College graduate Post graduate/professional % 1.10 9.89 17.58 23.08 36.26 12.09 – Randomly selected half of the individuals from the PACE intensive subgroup II. Methods Assessment Baseline assessment 10-Item Perceived Stress Scale – Cohen, Kamarck, & Mermelstein,1983 – “in the last week” Serum leptin (ng/mL) – UW Northwest Lipid Research Laboratory – Radioimmunoassay (RIA) II. Methods Analysis ■ Mixed Analysis – Continuous – Categorical – Independent Variable: 4 categories of stress – Dependent Variable: Serum Leptin ■ Leptin data log transformed ■ Covariates: – Worksite (random) – Gender and Body Mass Index (fixed) III. Results Descriptives: Mean (SD) Range Min Max Body Mass Index 29.99 (7.52) 34.78 18.15 52.93 Leptin (ng/mL) 16.98 (14.59) 56.7 1.0 57.7 Perceived Stress 11.76 (6.73) 28.0 1.0 29.0 III. Results ■ Stress entered as continuous predictor variable Perceived Stress Gender Body Mass Index F-value (df) p-value 0.14 (1,71) 50.09 (1,71) 118.10 (1,71) 0.71 0.001 0.001 III. Results ■ Stress entered as categorical variable Quartile Scores: Low (1-6) Moderate (11-15) Low Moderate (7-10) High (16-29) F-value (df) Perceived Stress Gender BMI 0.37 (3,69) p-value 0.78 48.93 (1,69) 0.001 117.95 (1,69) 0.001 III. Results Stress entered as categorical variable (cont.) t-value (df) p-value Quartile 1- Quartile 2 0.35 (69) 0.73 Quartile 1- Quartile 3 0.76 (69) 0.45 Quartile 1- Quartile 4 0.95 (69) 0.34 Quartile 2- Quartile 3 0.48 (69) 0.64 Quartile 2- Quartile 4 0.68 (69) 0.50 Quartile 3- Quartile 4 0.17 (69) 0.86 III. Results Effect of Gender Mean (SD) t-value p-value Men Women Body Mass Index 30.40 (5.46) 29.69 (8.73) 0.42 (78) 0.68 Leptin (ng/mL) 10.04 (8.16) 22.26 (16.31) -4.15 (78) 0.00 9.63 (6.01) 13.59 (6.67) -2.63 (78) 0.01 Perceived Stress III. Results ■ Stress entered as continuous predictor variable F-value (df) Perceived Stress 0.00 (1,70) Gender 22.55 (1,70) Perceived Stress*Gender 1.85 (1,70) Body Mass Index 122.07 (1,70) p-value 0.949 0.001 0.178 0.001 IV. Conclusion ■ No significant relationship between leptin and stress ■ Preliminary analyses conducted to determine appropriate sample size ■ Range of stress scores comparable to other studies ■ Menstrual cycle, use of medication, diet, etc. were not controlled IV. Conclusion ■ Changes in leptin may only be evident following acute stress ■ Higher levels of stress may be required to see a change in leptin levels ■ Action of chronic stress on immune function may not be mediated by leptin – leptin may not contribute to changes in the microenvironment of tumor cells IV. Future Directions ■ May want to consider – Stress type and duration – Dietary intake ■ CARB Study, Glycemic Load and Obesity Effects on Cancer Biomarkers (Neuhouser, M., Lampe, J.W., PI) ■ Health SMART, Stress Management and Relaxation Training (McGregor, B.A., PI) ■ Conduct additional analyses on PACE data Acknowledgements ■ Shirley Beresford, Ph.D. ■ Dale McLerran ■ Sonia Bishop ■ Bonnie McGregor, Ph.D.