Transcript Presentation

Ghrelin and obestatin
The gut-brain relationship
Authors: Mureșan Patricia
Kiss Szabolcs
L’Hoste Loïck
Coordinator: Julia Szakacs MD
What are you more afraid of?
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Contents
• Introduction
• Ghrelin
• Obestatin
• Discussion
• Ghrelin
• Obestatin
• Future resolutions
INTRODUCTION
• 1.9 billions of adults overweight
• 600 million obeses
• Increase the risk for several diseases
• Gut peptides: very active research field
for their implications in metabolism and
apetite
• Relation gut-brain also includes: mood,
stress and reward
GHRELIN
• 28 AA, Kojima et al (1999)
• From preproghrelin
peptide (stomach)
• GPR39
•
•
GH secretion and release ++
Effects:
•
•
•
•
OREXIGENIC
Food intake and body weight
CNS
Elevated levels before meals
“hormone
of
hunger”
A.Labarthe; O. Fiquet, R. Hassouna, P. Zizzari, L. Lanfumey et al, Ghrelin-derived peptides: a link between appetite/reward, GH
axis, and psychiatric disorders ? Frontiers in Endocrinology 5 (2014) 1-19.
BIOLOGICAL EFFECTS
• Food consumption
FOOD
Gh
OREXIGENIC
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• CNS effects
•
•
•
•
•
•
Memory
Learning
Motivation
Anxiolytic
Regulates mood
Alcohol and drug
consumption (enhanced;
blocked by GHSR1
antogonist)
• NEUROPROTECTIVE
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ANTAGONIST HORMONES
LEPTIN
ENDO
CANNABI
NOIDS
CCK
Orexigenic
effects
of
GHRELIN
PYY
OBESTATIN
OBESTATIN
• 23 AA, Zhang et al (2005)
• From preproghrelin peptide
Bachem pioneering partner for peptides: Ghrelin, leptin and obestatin
Obestatin related disorders
Disorder
Obesity
Anorexia nervosa
Obestatin
Negatively
correlated with BMI,
Insulin resistance
Index, plasma leptin
/
Depends on subtype
Anxiety and stress
?
A.Labarthe et al, Ghrelin-derived peptides: a link between appetite/reward, GH axis, and psychiatric disorders ? Frontiers in Endocrinology 5 (2014)
Discussion about ghrelin
• Controversy: Anxiolytic or Anxiogenic
K.P. Skibicka, S.L. Dickson, Enteroendocrine hormones – central effects on behavior, Current Opinion in Pharmacology. 13 (2013)
Discussion about ghrelin
• Important role in evolution (survival)
• Diseases related to ghrelin
• Anorexia
• Restrictive
• Binge-purging
• Treatments:
• Cachexia
• Obesity
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Discussion about obestatin
• Ultradian rhythmicity
• cplasma alters with nutritional status of the body
• Suggested signaling pathway: GHSR
CNS effects
Mood
Memory
retention
Anxiety
Obestatin
influences
the CNS ?
Motivation
Reward
CONCLUSION
• Obestatin: lack of knowledge ++
• Ghrelin:
• Agonist:
– anorexia
• Antagonist:
– Obesity
– Addiction
• Medication circuit vs Discovery of Ghrelin
Further research needed
• Ghrelin
• Mechanisms of ghrelin
• to modulate synapses (memory)
• To sensibilize to drugs and alcohol addictions
• Efficiency of the neuroprotection on diseases:
• Neurodegeneration
• Strokes
• Obestatin
• To find the receptor of obestatin
• To improve the present knowledge
Z.B. Andrews, The extra-hypothalamic actions of ghrelin on neuronal function, Trends in Neurosciences (2011)
THANK YOU FOR YOUR ATTENTION
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