Lecture 7.2: Control of Appetite

Question 1

What is a C-Peptide Test?

Answer 1

A C-peptide test is a blood test which is carried out to find out how much insulin your body is producing

Question 2

Why is a C-Peptide Test useful?

Answer 2

It may be useful for determining whether a patient has type 1 or type 2 diabetes or whether they have insulin resistance

Question 3

What is C-Peptide?

Answer 3

• C-Peptide is released at the same time as insulin
• For each molecule of insulin produced there is a molecule of C-Peptide
• C-Peptide does not itself influence blood sugar
• C-Peptide is a useful marker of insulin production because C-Peptide
tends to remain in the blood longer than insulin

Question 4

What does C-Peptide do?

Answer 4

It helps with the correct folding of insulin and in the formation of disulphide bonds

Question 5

Energy Balance: Intake and Expenditure

Answer 5

Intake: Carbohydrates, Lipids, Proteins
Expenditure: BMR, Physical Activity, Diet Induced Thermogenesis

Question 6

Energy Imbalance

Answer 6

Energy intake > Energy expenditure –> ↑ energy stores and body weight

Energy intake < Energy expenditure –> ↓energy stores and body weight

Question 7

Where is the appetite control centre?

Answer 7

Appetite Control Centre aka Satiety Centre

Located in the arcuate nucleus within the hypothalamus

Other brain areas are also involved in controlling appetite

Question 8

What Two Types of Neurones does the Arcuate Nucleus Contain?

Answer 8

Primary Neurones: sense metabolites in blood and respond to hormones

Secondary Neurones: receive input from primary neurones, co-ordinate a response

Question 9

Neurones of the Arcuate Nucleus

Answer 9

Two types of primary neurones:

Stimulatory (orexigenic) neurons: releasing Neuropeptide Y (NPY) and Agouti-related peptide (AgRP), promote hunger

Inhibitory (anorexigenic) neurons: releasing pro- opiomelanocortin (POMC) and cocaine and amphetamine-related transcript (CART), promote satiety

Question 10

Central Pathways in the Arcuate Nucleus

Answer 10

These central pathways are influenced by peripheral signals which stimulate or inhibit appetite (majority of them are inhibitory)

The central pathways interact with each other and feed into lateral hypothalamus

Lateral hypothalamus communicates with other parts of brain and influences the ANS and feeding behaviour

Question 11

Peripheral Signals: Appetite Stimulating

Answer 11

Ghrelin (stomach)

Question 12

Peripheral Signals: Appetite Suppressing (Pancreas) (3)

Answer 12

• Insulin (pancreas)
• Amylin (pancreas)
• Pancreatic polypeptide and enterostatin (pancreas)

Question 13

Peripheral Signals: Appetite Suppressing (Adipose Tissue)

Answer 13

• Leptin (adipose tissue)

Question 14

Peripheral Signals: Appetite Suppressing (Intestines) (4)

Answer 14

• Cholecystokinin (CCK) (duodenum and jejunum)
• Glucagon-like peptide (GLP-1) (ileum and colon)
• Peptide YY = peptide tyrosine tyrosine (PYY) (ileum and colon)
• Oxyntomodulin (colon)

Question 15

Signals From the Body to the Hypothalamus: Leptin

Answer 15

Polypeptide (145 aa) hormone released into blood from adipocytes

Stimulates the inhibitory primary neurones and inhibits the stimulatory primary neurones

Leptin induces expression of UCP in mitochondria leading to energy dissipation as heat

Overall effect is suppression of appetite, used clinically to treat obese patients lacking the hormone

Question 16

Signals From the Body to the Hypothalamus: Insulin

Answer 16

• Polypeptide (55 aa) hormone released to blood from β-cells
• Suppresses appetite by similar mechanism as leptin
• Seems to be less important than leptin in feeding

Question 17

Signals From the Body to the Hypothalamus: Amylin

Answer 17

Polypeptide (37 aa) hormone secreted by β-cells in pancreas

Roles not fully understood but known to suppress appetite, decrease glucagon secretion and slow gastric emptying

Pramlintide is an amylin analogue approved for treatment of Type 2 diabetes

Question 18

Signals from the Gut to the Hypothalamus: Ghrelin

Answer 18

Peptide (28 aa) hormone released from stomach wall when empty

Stimulates the stimulatory primary neurones in arcuate nucleus to promote appetite

Filling of stomach (distension) inhibits ghrelin release

Question 19

Signals from the Gut to the Hypothalamus: PYY/Peptide YY

Answer 19

Peptide (36 aa) hormone released from the ileum and colon in response to feeding

Inhibits the stimulatory primary neurones and stimulates the inhibitory neurones to suppress appetite

Question 20

Orexigenic Neurones: What are they? What hormones affect them? What neurotransmitters/receptors are involved?

Answer 20

Orexigenic neurones stimulate eating and are neuropeptide hormones

PYY (decrease), Ghrelin (increase), Leptin (decrease)

ARP & NYP neurotransmitters at synapse promote hunger

Question 21

Anorexigenic Neurones: What are they? What hormones affect them? What neurotransmitters/receptors are involved?

Answer 21

Anorexigenic neurones suppress the appetite

Leptin (increase), Insulin (increase)

αMSH (from POMC) acting at MC4 receptors promote satiety

Question 22

What are Incretins?

Answer 22

Incretins are gut-derived peptide hormones that are rapidly secreted in response to a meal

Incretins stimulate a decrease in blood glucose levels

Question 23

What are the two main incretins in humans?

Answer 23

Glucosedependent Insulinotropic Polypeptide (GIP)

Glucagon-Like Peptide-1 (GLP-1).

Question 24

Where are GIP and GLP-1 secreted from?

Answer 24

They are secreted from the intestine on ingestion of glucose or nutrients
to stimulate insulin secretion from pancreatic β cells

Question 25

What are GLP-1R and GIPR?

Answer 25

Glucagon-Like Peptide 1 Receptor (GLP-1R)
Glucosedependent Insulinotropic Polypeptide Receptor (GIPR)

Both are class B G protein-coupled receptors (GPCRs) which mediate the effects of GLP-1 and GIP respectively