Lecture 16. Receptors Linked to Enzymes

Question 1

How is BMI calculated?

Answer 1

BMI = weight (kg)/height (m²)

Question 2

What does a BMI > 30 mean?

Answer 2

Obese

Question 3

What does a BMI of 25-30 mean?

Answer 3

Overweight

Question 4

What does BMI < 25 mean?

Answer 4

Normal weight

Question 5

Why is BMI a poor measure?

Answer 5

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).

Question 6

What is an example of an extremely underweight country?

Answer 6

Ethopia

Question 7

What is an example of an extremely obese country?

Answer 7

Cook Islands

Question 8

What is obesity?

Answer 8

The result of intake of excess calories, more than are consumed by the body’s activities

Question 9

What are the mechanisms for dealing with excess calorific intake?

Answer 9

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

Question 10

What is the Lipostat theory?

Answer 10

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

Question 11

What occurs when adipose tissue decreases?

Answer 11

Feedback stimulates feeding behaviour (I’m hungry) and reduced fatty acid oxidation (let’s store it)

Question 12

What is released into the bloodstream by adipose tissue?

Answer 12

Leptin

Question 13

What does leptin do?

Answer 13

Leptin binds leptin receptors in the hypothalamus, and changes feeding behaviour (endocrine signalling)

Question 14

Where was leptin first identified?

Answer 14

In mice
The product of the Lepᴼᴮ(obese) gene
The number and size of adipocytes is increased in Lepᵒᵇ/Lepᵒᵖ mice

Question 15

What do Lepᵒᵇ/Lepᵒᵖ mice display?

Answer 15

The physiology and behaviour of starvation
Some similarities to Type II diabetes

Question 16

What does leptin correct?

Answer 16

The Lepᵒᵇ/Lepᵒᵖ phenotype

Question 17

What produces the leptin receptor?

Answer 17

The Leprᴰᴮ gene expressed in the hypothalamus

Question 18

What does leptin do?

Answer 18

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

Question 19

What are the effects of leptin on the body?

Answer 19

Suppression of appetite (eat less)
Stimulation of the sympathetic nervous system (do more)
Increased blood pressure
Increased heart rate
Increased thermogenesis

Question 20

What are JAKs?

Answer 20

Soluble kinases
Janus kinases ( JAKs) are cytosolic, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway

Question 21

What does leptin binding cause?

Answer 21

Dimerises Lep-R generating sites for the recruitments of JAKs

Question 22

What are STAT proteins?

Answer 22

Signal Transducer and Activator of Transcription are latent transcription factors that are activated by JAKS

Question 23

What does JAK phosphorylate?

Answer 23

Lep-R and phosphorylated Lep-R recruits STATs

Question 24

What STATs do JAKs phosphorylate?

Answer 24

‘Fat STATs’ STATs 3, 5 and 6

Question 25

How do fat STATs stimulate α-MSH expression?

Answer 25

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

Question 26

What is erythropoietin (EPO)?

Answer 26

A hormone cytokine that controls the development of erythrocytes (red blood cells) from precursor cells in the bone marrow

Question 27

What is the use of erythropoietin?

Answer 27

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.

Question 28

How does EPO signal?

Answer 28

1. Via a JAK-STAT pathway using STAT5
2. Following JAK autophosphorylation, EPO signalling can access a Ras-dependent pathway