Lecture 16. Receptors Linked to Enzymes Flashcards
How is BMI calculated?
BMI = weight (kg)/height (m²)
What does a BMI > 30 mean?
Obese
What does a BMI of 25-30 mean?
Overweight
What does BMI < 25 mean?
Normal weight
Why is BMI a poor measure?
It gives poor estimates for tall people (they appear to be too fat), for short people (they appear to be too thin) and for those with an athletic build (who appear to be too fat).
What is an example of an extremely underweight country?
Ethopia
What is an example of an extremely obese country?
Cook Islands
What is obesity?
The result of intake of excess calories, more than are consumed by the body’s activities
What are the mechanisms for dealing with excess calorific intake?
Conversation of excess fuel to fat that is stored
Increased locomotor activity: excess fuel is burnt by extra exercise
Thermogenesis: conversion of excess fuel to heat
What is the Lipostat theory?
Postulates that eating behaviour is inhibited when body weight exceeds a certain value (‘the set point’)
Postulates that energy consumption increases above the set point
Inhibition of eating behaviour and acids increased energy use should therefore reduce body mass back to the set point
What occurs when adipose tissue decreases?
Feedback stimulates feeding behaviour (I’m hungry) and reduced fatty acid oxidation (let’s store it)
What is released into the bloodstream by adipose tissue?
Leptin
What does leptin do?
Leptin binds leptin receptors in the hypothalamus, and changes feeding behaviour (endocrine signalling)
Where was leptin first identified?
In mice
The product of the Lepᴼᴮ(obese) gene
The number and size of adipocytes is increased in Lepᵒᵇ/Lepᵒᵖ mice
What do Lepᵒᵇ/Lepᵒᵖ mice display?
The physiology and behaviour of starvation
Some similarities to Type II diabetes
What does leptin correct?
The Lepᵒᵇ/Lepᵒᵖ phenotype
What produces the leptin receptor?
The Leprᴰᴮ gene expressed in the hypothalamus
What does leptin do?
It binds receptors in specific neurons (the anorexigenic or appetite-reducing neurons) in the hypothalamus, and stimulates a signalling cascade that results in release of a hormone ( α-MSH, alpha-melanocyte stimulating hormone) that modulates nervous transmission
What are the effects of leptin on the body?
Suppression of appetite (eat less)
Stimulation of the sympathetic nervous system (do more)
Increased blood pressure
Increased heart rate
Increased thermogenesis
What are JAKs?
Soluble kinases
Janus kinases ( JAKs) are cytosolic, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway
What does leptin binding cause?
Dimerises Lep-R generating sites for the recruitments of JAKs
What are STAT proteins?
Signal Transducer and Activator of Transcription are latent transcription factors that are activated by JAKS
What does JAK phosphorylate?
Lep-R and phosphorylated Lep-R recruits STATs
What STATs do JAKs phosphorylate?
‘Fat STATs’ STATs 3, 5 and 6
How do fat STATs stimulate α-MSH expression?
The phosphorylated STATs dimerise, exposing their nuclear localisation agents (NLS)
The dimerised STATs enter the nucleus dimerise, exposing their nuclear and are now active transcription localisation signals (NLS)
factors that modulate gene expression
The precursor for α-MSH is made and processed to produce α-MSH
What is erythropoietin (EPO)?
A hormone cytokine that controls the development of erythrocytes (red blood cells) from precursor cells in the bone marrow
What is the use of erythropoietin?
Erythropoietin analogues with iron injections are recommended as a possible treatment for anaemia caused by cancer treatment only in
Women receiving platinum-based chemotherapy for cancer of the ovaries who have a blood haemoglobin level of 8g/100 ml or lower
People who have very severe anaemia and cannot receive blood transfusions.
How does EPO signal?
- Via a JAK-STAT pathway using STAT5
- Following JAK autophosphorylation, EPO signalling can access a Ras-dependent pathway
