The physiology of feeding and satiety

Question 1

What is energy homeostasis?

Answer 1

A physiological process whereby energy intake is matched to energy expenditure over time.
It promotes body fuel stability - energy primarily stored as fat.

Question 2

What leads to obesity?

Answer 2

Accessible, tasty, calorie dense food + a sedentary lifestyle.
Obesity arises due to a small constant mismatch between energy intake and energy expenditure

Question 3

What BMI range is thin-normal?

Answer 3

Up to 25

Question 4

What BMI range is overweight?

Answer 4

25-29.9

Question 5

What BMI range is obese?

Answer 5

30 - 39.9

Question 6

What BMI range is morbidly obese?

Answer 6

At least 40

Question 7

Is the prevalence of obesity only in adults?

Answer 7

No- there is also an increased prevalence of obesity in children and young people.

Question 8

Why is the answer to obesity not as simple as changing our lifestyles to eat less fatty foods and do more exercise?

Answer 8

Because biological factors come into play.

Obesity is not a single disorder, but a heterogenous group of conditions with multiple causes.

Question 9

What are the major factors influencing obesity?

Answer 9

Genetic factors and environmental factors.
Genetics- this is usually through susceptibility genes, which increase risk of developing disease but are often not per se essential for disease expression.
Environment- unmask latent tendencies to develop obesity. Westernisation of diet.

Question 10

What diseases are obese people more at risk of developing?

Answer 10

Type 2 diabetes
High blood pressure
Heart attack
Certain cancers (colon)
Osteoarthritis

Question 11

Why is fat required by the body?

Answer 11

For energy storage and prevention of starvation.

It is also an energy buffer during prolonged illness.

Question 12

Why is it difficult to lose weight once it has been gained?

Answer 12

Increased body fat alters brain function.
Long-term obesity induces brain re-programming.
The result is, your brain views the extra weight (i.e. fat) as normal, and dieting as a threat to survival. Therefore it defends the new weight.

Question 13

How does the CNS influence energy balance and body weight?
What does the integration of these factors determine?
What is the site of integration of these?

Answer 13

1. Behaviour - feeding and physical activity
2. ANS activity- regulates energy expenditure
3. Neuroendocrine system- secretion of hormones

The integration of these determines feeding behaviour.
The site of integration is the brain, and the neural centre responsible is the hypothalamus.

Question 14

Give examples of conditions affecting the hypothalamus which can cause obesity or leanness.

Answer 14

Lesioning ventromedial hypothalamus causes obesity.

Lesioning lateral hypothalamus causes leanness.

Question 15

What underlies the control of energy intake and body weight?

Answer 15

1. Satiety signalling
2. Adiposity (the state of being obese) negative feedback signalling
3. Food reward

Question 16

What is the difference between satiation and satiety?

Answer 16

Satiation is the sensation of fullness generated during a meal.
Satiety is the period of time between the termination of one meal and the initiation of the next.

Question 17

What happens to satiation signals during a meal?

Answer 17

They increase, to limit the size of the meal.

Question 18

Name and describe 5 satiation signals.

Answer 18

1. Cholecystokinin: secreted from enteroendocrine cells in the duodenum and jejunum. It is released in proportion to lipids and proteins in the meal. It signals to the hindbrain via sensory nerves and stimulates the hindbrain directly in the nucleus of the solitary tract (NTS).
2. Peptide YY- secreted from endocrine mucosal L-cells of the GI tract. Levels increase rapidly post-prandially. It inhibits gastric motility, slows emptying and reduces food intake. It signals to the hypothalamus.
3. Glucagon-like peptide 1- a product of the pro-glucagon gene. It is also released from L-cells in response to food ingestion. It inhibits gastric emptying and reduces food intake. It signals to the hypothalamus.
4. Oxyntomodulin- also from the pro-glucagon gene and released from oxyntic cells of the small intestine after a meal. It acts to suppress appetite, though the mechanism is unclear.
5. Obestatin- a peptide produced from a gene that encodes ghrelin and released from cells lining the stomach and the small intestine. It has been suggested to reduce food intake (possibly by antagonising the actions of Ghrelin), though its actions are unclear at present.

Question 19

What is Ghrelin?

Answer 19

A peptide produced and secreted by oxyntic cells in the stomach. Ghrelin levels increase before meals and decrease after meals. Levels are raised by fasting and hypoglycaemia.
Peripheral Ghrelin stimulates food intake (by signalling to the hypothalamus) and decreases fat utilization.

Question 20

Is weight generally stable or unstable for long periods of time?
Is this the case for lean or obese people?

Answer 20

Weight is generally stable in humans over long periods of time, and this is true for both lean and obese people.

Question 21

How is overall energy balance controlled over long periods of time?

Answer 21

By feedback loops which act to maintain constancy of total body energy stores.
The signals are produced in response to body nutritional status. They are sensed in the hypothalamus, which acts to modulate food intake and energy expenditure.

Question 22

What increases food intake when injected into hypothalamic centres? How long is the effect?

Answer 22

Glutamate, Gaba and opioids

The effects are modest and short lasting

Question 23

What act to suppress food intake?

Answer 23

Monoamines

Question 24

What two hormones send “adiposity” signals to the hypothalamus?
Where are they produced?
What is the purpose of this signalling?
What is different about it in obesity?

Answer 24

Leptin and insulin.
They are produced in peripheral tissues.
Leptin ismade and released from fat cells.
Insulin is made and released from pancreatic cells.
The purpose of this signalling is to communicate the status of fat stores to the brain, in order to control the amount of body fat. They inform the hypothalamus to alter energy balance by eating less and increasing energy burn.
In the obese state, the function of leptin and insulin malfunctions.

Question 25

How do the levels of leptin and insulin change as more fat is stored?

Answer 25

The levels of leptin and insulin in the blood increase as more fat is stored.

Question 26

What is the effect of reduced leptin?

Answer 26

It mimics starvation, causing an unrestrained appetite.

Question 27

What is the effect of mutation of the leptin receptor?

Answer 27

There is a whole body loss of leptin signalling. This results in severe obesity.

Question 28

What are the biological roles of leptin?

Answer 28

Food intake/energy expenditure/fat deposition
Peripheral glucose homeostasis/insulin sensitivity
Maintenance of the immune system
Maintenance of the reproductive system
Angiogenesis
Tumourigenesis
Bone formation

Question 29

What are the levels of circulating insulin like in relation to adiposity?

Answer 29

They are proportional

Question 30

What does intracerebroventricular insulin do?

Answer 30

It inhibits food intake

Question 31

What is the effect of neuron-specific deletion of the insulin receptor?

Answer 31

Obesity

Question 32

What types of food are linked to the hedonistic aspect of eating?

Answer 32

Sugar and fat

Question 33

What are leptin levels like in the vast majority of human obesity?
What limits the therapeutic use of leptin?

Answer 33

Very high, in correlation with fat levels.
The use of leptin therapeutically is limited by severe leptin resistance which is present in most obese individuals.
Diet induced obesity results in leptin resistance.

Question 34

What are the two main theories for diet induced obesity causing leptin resistance?

Answer 34

1. Defective leptin transport into the brain

2. Altered signal transduction following leptin binding to its receptor.

Question 35

Name two drugs currently prescribed for the treatment of obesity.
Which of these has been withdrawn?

Answer 35

Sibutramine (meridia and reductil) (this has now been withdrawn in several countries including the UK)
Orlistat (Xenical or Alli)

Question 36

What does Sibutramine do?

Why has it been withdrawn?

Answer 36

It selectively inhibits the re-uptake of noradrenaline, 5-HT and dopamine.
It decreases food intake and may also increase thermogenesis.
Concerns over side effects- CV events and strokes

Question 37

How does orlistat treat obesity?
What are its side effects?
What should be taken alongside it?

Answer 37

It inhibits pancreatic lipase and therefore limits TAG absorption.
The side effects are cramping and diarrhoea.
Vitamin supplements should also be taken.

Question 38

What are the effects of gastric bypass surgery?

Answer 38

Produces substantial weight loss in one year that is sustainable and significantly reduces mortality
In most cases it resolves T2D by reversing insulin resistance
The by pass restricts calorie intake and induces malabsorption of nutrients

Question 39

What would be the effect of inducible browning of WAT?

Answer 39

This could promote adaptive thermogenesis, where there is uncoupling of oxidative metabolism from ATP production, as the uncoupling protein short circuits the proton gradient produced in mitochondria, so less ATP is produced.
The energy is diffused as heat instead.