Stress, Obesity and Mental Health: The ghrelin Connection
Acknowledgements
Abizaid lab
Elaine Waddington Lamont
Samantha King
Rim Khazall
Zack Patterson
Ian Blum
Martin Wellman
Harry McKay
Val Charbonneau
Trevor Rodrigues
Jen Bruton
Veronique St. Onge
Collaborators
Hymie Anisman
Tamas Horvath
Marina Picciotto
Mark Sleeman
Supported by
NSERC, CFI & CIHR
Carleton University
Learning Objectives:
• Describe how metabolic hormones are related to
stress responses
• Describe how ghrelin is secreted in response to stress to produce
obesity in laboratory models.
• Decribe how this response is adaptive and how lack
of this response Leads to vulnerability to mental health disorders
Stress tip the energy balance
equation into the negative
What does ghrelin have to do with this?
Kojima et al (1999). Ghrelin is a growth‐hormone‐
releasing acylated peptide from stomach. Nature 402, 656‐660.
synthetic peptide
bioactive
ghrelin
+
n-octanoic acid
Ghrelin responsive neuronal targets
Are found in regions of the brain regulating energy balance, stress responses and reward seeking behaviors
Hypothesis: Does ghrelin
mediate stress‐induced obesity?
Chronic Social Defeat increases ghrelin concentrations
300
250
200
Control
20
Stress
18
16
14
12
150
100
50
10
8
6
4
2
0
0
Average Body Weight (g)
32
Control
30
Stress
28
Control
Stress
*
*
26
24
22
Average caloric intake (kcal)
20
18
16
14
12
10
8
6
4
2
0
*
*
R‐19
R‐16
R‐13
R‐10
R‐7
R‐4
R‐1
S‐19
S‐16
S‐13
S‐10
S‐7
S‐4
S‐1
B‐16
B‐13
B‐10
B‐7
B‐4
B‐1
Average 4 hour High Fat Intake (g)
Average Chow Intake (g)
Figure 2 (cont)
4.5
4
3.5
3
2.5
2
*
1.5
1
*
0.5
0
3
2.5
2
1.5
*
1
0.5
0
Baseline
Stress
Recovery
Figure 3
*
Average Daily Caloric
Intake (Kcal)
2.5
2
1.5
1
0.5
Plasma Active Ghrelin (pg/ml)
0
*
350
300
250
200
150
100
50
0
WT control WT Stress KO Control KO Stress
¶
20
15
10
5
0
WT control WT Stress KO Control KO Stress
450
400
25
Plama Corticosterone (µg/dl)
Weight Gain (g)
3
WT control WT Stress KO Control KO Stress
12
10
*
*
8
6
4
2
0
WT control WT Stress KO Control KO Stress
Figure 4
Figure 6
Visceral Fat
1
Brown Fat
**
0.9
Weight (g)
0.8
0.7
0.6
*
0.5
0.4
0.3
0.2
0.1
0
WT-NS
WT-S
KO-NS
KO-S
Adipocyte Size (μm)
Figure 6 (cont)
400
350
300
250
200
150
100
50
0
Ghrelin is a stress hormone and
it protects against depression
SUMMARY
• Stress changes metabolism as an adaptive response
• Ghrelin plays an important role in these changes
• Chronic stress may lead to obesity via long term changes in metabolism
• Insensitivity to ghrelin leads to vulnerability to stress induced depressive like behaviors in mice