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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.