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Stress-induced endocrine responses and anxiety: the effects of comfort food
Regina Célia Spadari
2nd International Conference on Endocrinology
Chicago - October 19-22
Obesity
• Prevalence of overweight and obesity.
• In the USA approximately two thirds of the population is overweight, and nearly one third is obese.
• The causes of the epidemic obesity are complex, and stress has been identified as an important factor.
Flegal et al., 2010
• Increased rates of obesity have been accompanied by a concomitant rise in perceived stress in North America.
Peripheral Stress System
SNS
NE NE
Adrenal medulla
epinephrine
norepinephrine
Hypothalamus (PVN)CRH
Pituitary (anterior)ACTH
Adrenal cortexCortisol/Corticosterone
Components of stress system
Tomiyama et al., 2011
Epel et al., 2004
One subset of the population increases food intake under stress and
conversely, another decreases food intake. Block et al., 2009
Foster et al., 2009; la Fleur et al., 2005
Stress and food preference
• Access to sucrose reduces the activation of the HPA axis in response to
stress.
Foster et al., 2009
• Consumption of more palatable food improves emotional states, as
reflected by reduced anxiety- and depressive-type behaviors.
Maniam and Morris, 2010Ulrich-Lai et al., 2010
• Foot shock stress – short-term stress (120 electric paw shock; 1 mA, 1 s;
30 min/day; 3 consecutive days).
• Chronic unpredictable mild stress (CUMS) – 14 days.
• Cafeteria diet
• High carbohidrate
• High lipids
Ortolani et al., 2011; 2014
Regular chow + comfort food
Stress models used in the Laboratory of Stress Biology
• light intensity: 60 lux, behavior was registered during 5 min.
Analized parameters: •number of entries •time spent in the open and closed arms•number of head dipping, rearing, fecal bolus, stretched-attend posture, risk assessment and grooming.
Analized parameters: •latency of first crossing, •time spent in the periphery and in the center•number of crossing, rearing, grooming and fecal bolus.
Behavioral analysis
EPM EZM OF
Ortolani et al., 2011
• Activation of autonomic nervous system;• Release of CRH, ACTH, glucocorticoids, leptin and insulin.
Many factors may be envolved:
The mechanisms have not been clarified yet
Foot shock stress reduces the intake of regular chow but not that of comfort food
Ortolani et al., 2014
CUMS reduces the intake of commercial chow and comfort food
Ortolani et al., 2011; 2014
Comfort food intake attenuates endocrine response to foot shock stress and CUMS
Ortolani et al., 2011
• Foot shock stress reduces anxiety-like behaviors – EPM.
• This effect is not altered by comfort food.
Ortolani et al., 2011
• Foot shock stress reduces anxiety-like behaviors – EPM.
• This effect is not altered by comfort food.
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Ortolani et al., 2011
• Foot shock stress associated to comfort reduces anxiety-like
behaviors - open field.
• CUMS (14 days) induces anxiety-like behavior - EPM.
• This effect is not altered by comfort food.
Ortolani et al., 2014
• CUMS (14 days) induces anxiety-like behavior - open field.
• This effect is not altered by comfort food.
Ortolani et al., 2014
Conclusions
The access to comfort food attenuates the corticosterone
response to stress but did not prevent anxiety-like behaviors of
rats exposed to chronic stress.
• Chronic oral corticosterone was recently reported to induce impressive metabolic changes in mice including weight gain, increased adiposity, elevated plasma leptin, insulin and triglyceride levels, and hyperphagia (Karatsoreos et al., 2010).
• This model has the added benefit of result in a late-night increase in plasma corticosterone, mimicking one of the most predictive factors in Cushing’s syndrome (Yaneva et al., 2004).0
Sarabdjitsingh et al., 2012
HCM system
17.9 ug/day/g corticosterone or vehicle (1% ethanol solution) in the
drinking water during a 14 day monitoring period.
20
22
Orexigenic Anorexigenic
Co-expressed in arcuate nucleus neurons
*
mRNA expression of hypothalamic genes
23
Daily food intake Daily liquid intake
Results
Locomotor activity in the PAS equipment
EZM analysis
EZM analysis
Novel object analysis
Blue line: control groupGreen line: CORT group
27
Red line: control groupBlue line: CORT group
28
Bout size
Red line: control groupBlue line: CORT group
Red line: control groupBlue line: CORT group
Red line: control groupBlue line: CORT group
Chronic CORT treatment alters components of behavioral patterns and their circadian regulation, and results in a phenotype that mimics the metabolic syndrome.
•CORT-induced suppression of DC activity is mediated by a selective suppression of AS duration, rather than changes in locomotion bout properties.
•CORT-induced enhancement of feeding arrives from a selective increase in feeding bout size driven by prolonged feeding bout durations.
•These findings suggest a deficit in satiation or the process that terminates a meal in CORT-treated mice.
•Chronic CORT treatment suppressed exploration of a novel object, a finding consistent with an enhancement of anxiety-related behavior.
Conclusions
Spadari’s Lab – Laboratory of Stress Biology (Federal University of Sao Paulo, Santos, Brazil)
Acknowledgments
Dr. Laurance Tecott (University of California, San Francisco, CA, USA)
Financial Support: Judith Rose Shea Foundation and FAPESP
Acknowledgments
Chronic unpredictable mild stress (CUMS): 14 days
Moreau et al., 1994; Ortolani et al., 2014
Period Monday Tuesday Wednesday Thursday Friday
Morning Restraint (30 min)
Restraint(30 min)
Food restriction
Empty water bottle (60 min)
Restraint (30 min)
Restraint (30 min)
Afternoon Restraint (30 min)
Restraint (30 min)
Restraint (30 min)
Restraint (30 min)
NightLight on
during the night
Water/food deprivation overnight
Water deprivation overnight
Damp sawdust overnight
Inversion of the
light/dark cycle over weekend
Comfort food
Cafeteria food: commercial chow (Labina, Purina®, Grupo Evialis), peanuts (Hikari®, São Paulo), milk chocolate (Chocolates Garoto®) and biscuit (Tostines®, Nestlé).
Components Commercial Chow Comfort Food
Protein 23,5% 20%
Lipid 4,6% 20%
Carbohidrate 33,4% 48%
Fiber 11,4% 4%
Total Caloric Value 17,03 kJ/g 21,40 kJ/g
Ortolani et al., 2011; 2014
