Hypothalamus, Leptin Signalling and Resistance Flashcards
What neurons does the melanocortin circuit comprise?
First order neurons:
Neuropeptide Y, AGRP, POMC
Roles of leptin in whole body homeostasis
Feeding - eating
Anorexia - starvation
Hedonic feeding - motivation to eat
Energy expenditure - thermoregulation
Glucose homeostasis - insulin sensitivity
True or false:
ARC neurons/circuits are crucial for fat (energy) and glucose homeostasis
True
What hormones are involved in surveillance of total body energy stores?
Leptin and Insulin by targeting the ARC neurons
Leptin and insulin are increased/decreased in the fasted state
Decreased
Leads to activation of NPY/AGRP and inhibits POMC
Leptin and insulin are increased/decreased in the fed state
Increased
Leads to inhibition of NPY/AGRP and activates POMC
What does ghrelin act in opposition to?
Acts in opposition to leptin/insulin in the ARC
What secretes ghrelin?
Endocrine cells lining the stomach
What is the enzyme that makes ghrelin active?
GOAT - ghrelin-O-acetyltransferase
Are ghrelin levels high before or after a meal?
Before, they rapidly fall after eating.
Is ghrelin the direct cause of obesity?
No
What are the results of chronic ghrelin infusion to the CNS?
Increased lipogenesis, decreased lipid oxidation
Increases blood glucose and decreases insulin secretion
DIO increases/reduces ghrelin secretion, plasma ghrelin, GOAD mRNA and transport across the BBB
Reduces
What becomes resistant to ghrelin during obesity?
The hypothalamic circuitry (ARC: NPY/ARGP neurons) that controls food intake
True or false:
Ghrelin levels normalise quickly when weight loss is achieved
False
They take a very long time to normalise
What is the physiological role of ghrelin?
To defend the body weight and glucose homeostasis during times of food shortage to prevent weight loss
What does LEAP2 do?
Blocks the effects of ghrelin in a dose dependent manner
Does fasting reduce or increase LEAP2 levels?
Reduces
Re-feeding increases
In obesity there is higher/lower LEAP2 and higher/lower ghrelin
There is higher LEAP2 and lower ghrelin
Leptin, insulin and ghrelin activate signalling pathways to trigger responses by what?
Transcription of neuropeptides
Electrical activity
Synaptic plasticity
Key signalling pathways in energy and glucose homeostasis
JAK-STAT
PI3K-FoxO1
AMPK
Shp-MAPK
True or false:
Leptin receptors do not have intrinsic tyrosine kinase
True
Describe the structure of leptin receptors
Single transmembrane domain cytokine-like protein
Has to have a dimer
End-terminal domain
What happens when leptin binds to the leptin receptor?
You get dimerisation