Obesogenic Enviornment

Question 1

What is NPY and what does it do?

Answer 1

Neuropeptide Y is a 36 chain amino acid and is one of the most abundant in then human brain.

Injection of NPY into the hypothalamus

• stimulates food intake
• Reduces energy expenditure
• Induces lipogenic enzymes in fat and liver cells

There are a significant number of NPY containing neurones in the ARC and DMN.

Question 2

What happens to mice lacking in NPY receptor subtypes (Y1 and Y5) ?

Answer 2

They are predisposed to mild obesity - this may seem the opposite of wehat you would expect but it is due to:

• functional redundancy
• developmental compensation

Question 3

What do NPY receptor antagonists do?

Answer 3

Attenuate feeding and therefore reduce weight gain.

Question 4

What is aMSH and what does it do?

Answer 4

a Melanocyte-stimulating hormone is a non-opiod peptide encoded by the POMC gene. aMSH levels are high in the hypoythalamus (arcuate) and inhibits food intake.

POMC gene expression is:

• Reduced on fasting
• Increased follwing attainment of positive energy balance

Question 5

Agonists and antagonists of Melanocirtin receptior substypes (MC-3 and MC-4) do what respectively?

Also what does deletion of these receptor subtypes cause?

Answer 5

Agonists - Suppress food intake

Antagonists - Enhance food intake

Deletion will cause obesity in mice.

Question 6

Describe the locaiton of NPY and POMC neurones.

Answer 6

there are high levels of NPY and POMC neurones in the arcuate nucleus. Both sets of neurones send off projections onto other areas ofg the hypothalamus such as the PVN (paraventricular nucelus) and the LHA/PFA (Lateral hypothalamus and perifornical area)

Question 7

What is AgRP and what does it do?

Answer 7

Agouti-related protein is an analogue of agouti, a colour coat regualting protein. The agouti protein induces obesity by antagonising the action of aMSH on MC-receptors.

Expression of AgRP is limited in the ARC where it antagonises (actually an inverse agonist) MC-3 and MC-4.

AgRp is co-expressed with NPY in ARC neurones

Question 8

What is an inverse agonist?

Answer 8

A drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist, by suppressing spontaenous receptor signalling.

Question 9

What is CART and what does it do?

Answer 9

Cocaine and Amphetamine Regulated Transcipt. Anorexogenic neuropeptide, the mRNA of which can be increased through the use of cocaine and amphetamine.

• Inhibits feeding (short acting)
• Increased locomotor activity

Found throughout the CNS inclusing the hypothalamic centres ARC, VMH, PVN.

CART is coexpressed with aMSH in ARC POMC neurones.

Question 10

Lesions in which areas of the hypothalmaus cause obesity and anorexia respectively?

Answer 10

VMH - Ventromedial hypothalamus lesion causes obesity

LHA - Lateral hypothalamus lesion causes anorexia.

Lateral Lesion Leaness

Question 11

The PVN regulates pituitary hormone secretion. Give examples of this.

Answer 11

TRH - Thyrotropin releasing hormone neurones that stimulates the secretion of TSH and prolatin in the anterior pituiatary.

CRH - Corticotrophin releasing hormone synthesised in the PVN controls ACTH secretion in the anterior pituitary. CRH in the PVN elicits:

• reduced food intake
• increased sympathetic outflow
• Increased energy expenditure

(think of cortisol effects)

These neurosecretory cells are classified as parvocellular.

Question 12

Two major peptigergic neurones in the LHA are important to energy homeostasis. What are they?

Answer 12

MCH - Increases food intake. Deficient mice are hyperactive, lean and eat less.

Orexins (hypocretins) - Central injection of either orexin-A or orexin-B causes increased food intake

Question 14

What are satiation signals ? Give some examples of the neutrotransmitters involved.

Answer 14

Satiation signals increase during meals to limit meal size.

CCK

PYY

GLP-1

OXM

Obestatin