Flashcards in The physiology of feeding and satiety Deck (39):
What is energy homeostasis?
A physiological process whereby energy intake is matched to energy expenditure over time.
It promotes body fuel stability - energy primarily stored as fat.
What leads to obesity?
Accessible, tasty, calorie dense food + a sedentary lifestyle.
Obesity arises due to a small constant mismatch between energy intake and energy expenditure
What BMI range is thin-normal?
Up to 25
What BMI range is overweight?
What BMI range is obese?
30 - 39.9
What BMI range is morbidly obese?
At least 40
Is the prevalence of obesity only in adults?
No- there is also an increased prevalence of obesity in children and young people.
Why is the answer to obesity not as simple as changing our lifestyles to eat less fatty foods and do more exercise?
Because biological factors come into play.
Obesity is not a single disorder, but a heterogenous group of conditions with multiple causes.
What are the major factors influencing obesity?
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.
What diseases are obese people more at risk of developing?
Type 2 diabetes
High blood pressure
Certain cancers (colon)
Why is fat required by the body?
For energy storage and prevention of starvation.
It is also an energy buffer during prolonged illness.
Why is it difficult to lose weight once it has been gained?
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.
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?
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.
Give examples of conditions affecting the hypothalamus which can cause obesity or leanness.
Lesioning ventromedial hypothalamus causes obesity.
Lesioning lateral hypothalamus causes leanness.
What underlies the control of energy intake and body weight?
1. Satiety signalling
2. Adiposity (the state of being obese) negative feedback signalling
3. Food reward
What is the difference between satiation and satiety?
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.
What happens to satiation signals during a meal?
They increase, to limit the size of the meal.
Name and describe 5 satiation signals.
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.
What is Ghrelin?
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.
Is weight generally stable or unstable for long periods of time?
Is this the case for lean or obese people?
Weight is generally stable in humans over long periods of time, and this is true for both lean and obese people.
How is overall energy balance controlled over long periods of time?
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.
What increases food intake when injected into hypothalamic centres? How long is the effect?
Glutamate, Gaba and opioids
The effects are modest and short lasting
What act to suppress food intake?
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?
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.
How do the levels of leptin and insulin change as more fat is stored?
The levels of leptin and insulin in the blood increase as more fat is stored.
What is the effect of reduced leptin?
It mimics starvation, causing an unrestrained appetite.
What is the effect of mutation of the leptin receptor?
There is a whole body loss of leptin signalling. This results in severe obesity.
What are the biological roles of leptin?
Food intake/energy expenditure/fat deposition
Peripheral glucose homeostasis/insulin sensitivity
Maintenance of the immune system
Maintenance of the reproductive system
What are the levels of circulating insulin like in relation to adiposity?
They are proportional
What does intracerebroventricular insulin do?
It inhibits food intake
What is the effect of neuron-specific deletion of the insulin receptor?
What types of food are linked to the hedonistic aspect of eating?
Sugar and fat
What are leptin levels like in the vast majority of human obesity?
What limits the therapeutic use of leptin?
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.
What are the two main theories for diet induced obesity causing leptin resistance?
1. Defective leptin transport into the brain
2. Altered signal transduction following leptin binding to its receptor.
Name two drugs currently prescribed for the treatment of obesity.
Which of these has been withdrawn?
Sibutramine (meridia and reductil) (this has now been withdrawn in several countries including the UK)
Orlistat (Xenical or Alli)
What does Sibutramine do?
Why has it been withdrawn?
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
How does orlistat treat obesity?
What are its side effects?
What should be taken alongside it?
It inhibits pancreatic lipase and therefore limits TAG absorption.
The side effects are cramping and diarrhoea.
Vitamin supplements should also be taken.
What are the effects of gastric bypass surgery?
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