Stress-induced endocrine responses and anxiety: the effects of comfort food

1
2nd International Conference on
Endocrinology Chicago - October 19-22
Stress-induced endocrine responses and anxiety
the effects of comfort food
Regina Célia Spadari
2
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.

• Increased rates of obesity have been accompanied
  by a concomitant rise in perceived stress in
  North America.

Flegal et al., 2010
3
Components of stress system
Peripheral Stress System
Hypothalamus (PVN) CRH
SNS
NE
NE
Pituitary (anterior) ACTH
Adrenal medulla
epinephrine norepinephrine
Adrenal cortex Cortisol/Corticosterone
4
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
5
Stress and food preference
Foster et al., 2009 la Fleur et al., 2005
6

• 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, 2010 Ulrich-Lai et al., 2010
7
Stress models used in the Laboratory of Stress
Biology

• 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.

Regular chow comfort food

• Cafeteria diet
• High carbohidrate
• High lipids

Ortolani et al., 2011 2014
8
Behavioral analysis
EPM
EZM
OF

• 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.

9
Foot shock stress reduces the intake of regular
chow but not that of comfort food
Ortolani et al., 2011
Many factors may be envolved

• Activation of autonomic nervous system
• Release of CRH, ACTH, glucocorticoids, leptin
  and insulin.

The mechanisms have not been clarified yet
10
CUMS reduces the intake of commercial chow and
comfort food
Ortolani et al., 2014
11
Comfort food intake attenuates endocrine
response to foot shock stress and CUMS
Ortolani et al., 2011 2014
12

• Foot shock stress reduces anxiety-like behaviors
  EPM.
• This effect is not altered by comfort food.

Ortolani et al., 2011
13

• Foot shock stress reduces anxiety-like behaviors
  EPM.
• This effect is not altered by comfort food.

Ortolani et al., 2011
14

• Foot shock stress associated to comfort reduces
  anxiety-like behaviors - open field.

Ortolani et al., 2011
15

• CUMS (14 days) induces anxiety-like behavior -
  EPM.
• This effect is not altered by comfort food.

Ortolani et al., 2014
16

• CUMS (14 days) induces anxiety-like behavior -
  open field.
• This effect is not altered by comfort food.

Ortolani et al., 2014
17
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.
18

• 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
  Cushings syndrome (Yaneva et al., 2004).0

Sarabdjitsingh et al., 2012
19
HCM system
17.9 ug/day/g corticosterone or vehicle (1
ethanol solution) in the drinking water during a
14 day monitoring period.
20
(No Transcript)
21
(No Transcript)
22
mRNA expression of hypothalamic genes
Orexigenic
Anorexigenic

Co-expressed in arcuate nucleus neurons
23
Results
Daily food intake
Daily liquid intake
24
Locomotor activity in the PAS equipment
25
EZM analysis
26
EZM analysis
Novel object analysis
Blue line control group Green line CORT group
27
Red line control group Blue line CORT group
28
Red line control group Blue line CORT group
29
Red line control group Blue line CORT group
30
Red line control group Blue line CORT group
31
Conclusions

• 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.

32
Acknowledgments
Spadaris Lab Laboratory of Stress Biology
(Federal University of Sao Paulo, Santos, Brazil)
33
Acknowledgments
Dr. Laurance Tecott (University of California,
San Francisco, CA, USA)
Financial Support Judith Rose Shea Foundation
and FAPESP
34
Thank you!
regina.spadari_at_unifesp.br
35
Chronic unpredictable mild stress (CUMS) 14 days
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)  
Night Light on during the night Water/food deprivation overnight Water deprivation overnight Damp sawdust overnight Inversion of the light/dark cycle over weekend
Moreau et al., 1994 Ortolani et al., 2014
36
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