Cardio 3 Flashcards
What does white adipose tissue secrete and what does this signal by?
Leptin - ObR receptor via POMC
What pathway does leptin activate?
JAK-STAT
What does JAK-STAT lead to?
Cell growth and proliferation
What does MAPK lead to?
Cell growth and differentiation
What does PI3K lead to?
Growth, proliferation and differentiation
What happens when megalin binds to leptin?
Signalling cascade
What is the main perpetrator for increased BP associated with obesity?
Leptin
What happens to leptin levels when on high fat diet?
Increase
What does abnormal leptin signalling cause?
Obesity
What happens if you change the leptin pathway?
No obesity associated hypertension
What happens if the leptin concentration is restored?
Heart rate and hypertension increased
What does leptin target in the brain?
DMH to regulate BP
What happens if you turn off leptin signalling via leptin receptor?
Prevent increased BP
Is leptin present in the urine in obesity?
No - kidneys able to process leptin
What does leptin do to the glomerulus?
Alters it - increases TGF-B1 - increases collagen and fibrosis
What happens when proximal tubule cells are exposed to more leptin?
More phosphorylated and active proteins - megalin signals by mTORC2 instead of JAK-STAT
What proteins does the glomerulus filter?
Proteins less than 70kda - including albumin
What % of albumin is filtered and reabsorbed?
0.06-3%, 96%
What is the function of podocytes?
Allow selective passage of contents into the filtrate
What is megalin?
Scavenger receptor in proximal tubule that binds to ligands
What is the function of megalin?
Bring ligands into cell for degradation or transcytosis
What does the amount of megalin determine?
The quantity of proteins that will be degraded
What does meaglin do when cleaved by peptide transferases?
Acts as a signal transducer - regulates gene transcription
What does AMPK do?
Regulates cell energy homeostasis
What activates AMPK?
Leptin and adiponectin
What does obesity do to AMPK?
Blocks it - increases inflammation
What does activation of AMPK in type 2 diabetes prevent?
Renal hypertophy
What does AMPK inhibition decrease?
TGF-B1 secretion
What is AMPK the driver for, and what is this initiated by?
Fibrotic change - leptin binding to megalin
Where is leptin secreted from and what is the normal plasma level?
Secreted from placenta, GIT, mammary epithelium
Normal concentration is 59.5ng/mL
What is the direct action of leptin and why?
Increase BP - activation of nerves that supply CV system
What does leptin up regulate in the proximal tubule cells?
ERK 1/2, AMPK, mTOR
What % of Australians are obese?
63%
How does leptin reduce metabolic activity?
mTOR
