Cardiovascular Health Lecture 1.3 : Role of leptin in cardiorenal function Flashcards
What releases leptin?
Adipocytes.
What happens to leptin secretion in obese subjects?
Increases.
What is the main effect of leptin?
Decreases hunger and increases satiety.
If obese people have a 2-3 fold increase n leptin, why do they still become hungry?
Obese people have leptin resistance, so don’t have reduced hunger or increased satiety.
What is the receptor of leptin?
OBRb.
Which neurons are OBRb receptors found, and what effect do they have?
POMC neuron - decreased food intake
NPY neuron - increased food intake
What happens with an imbalance of POMC and NPY neuron activation?
Weight gain or loss.
What happens when leptin binds to OBRb?
Jak2 phosphorylates, and activates STAT3, which dimerises. Both STATs phosphorylate, localise to the nucleus and induce gene activation.
What pathways does OBRb activate (name 3)?
JAK/STAT pathway
MAPK pathway
PI3K pathway
What effect does leptin have on blood pressure?
Increases it.
What happens to leptin levels in obese subjects on a low fat diet?
Decreases.
What happens to knockouts of leptin or the OBRb receptor? Why? What happens if on a high fat diet?
Develop obesity soon after birth.
No normal leptin signalling, and nothing to regulate hunger causes this.
A high fat diet increases obesity further.
What happens to heart rate in a knockout of leptin or OBRb receptor? Why?
No increase in heart rate.
Hypertension associated with obesity isn’t present if leptin pathway isn’t functioning normally.
What happens to blood pressure if leptin is supplemented to leptin knockouts?
Hypertension returns.
What happens to blood pressure if leptin or OBRb receptors are inhibited/blocked?
Blood pressure returns to normal.
Does the glomerulus discriminate by size alone? Explain.
No, not always. Generally under 70kDa is filtered through, but not all.
What is megalin?
Scavenger receptor in the proximal tubule of kidneys.
Does megalin bind to leptin?
Yes, amongst many other proteins.
What does megalin do to proteins it binds to?
Degrades them or takes them in via transcytosis.
What is the rate limiting step in degredation or transcytosis of proteins by megalin?
Amount of megalin on the membrane.
What does megalin do if cleaved?
Can localise to the nucleus to induce genes.
Does leptin get filtered? What happens after?
Yes it does, gets taken up by megalin.
Do obese people secrete leptin?
No.
What happens to the glomerulus with high levels of leptin, and what effect does this have?
Fibrotic, reducing filtering capacity.
More proteins filter through.
