Energy balance and control of food intake

Question 1

What is a positive energy balance?

Answer 1

More energy intake than expenditure

Question 2

What is a negative energy balance?

Answer 2

Energy expenditure higher than intake

• can lead to weight loss
• subject is oxidising endogenous carbohydrate, fat and or/ protein reserves

Question 3

What is the homeostatic regulation of appetite?

Answer 3

The homeostatic pathway controls energy balance by increasing the motivation to eat following the depletion of energy stores
- hunger

Short-term signals –> meal related
Long-term signals –> adipose related

Depletion of energy stores –> high levels of peripheral ghrelin –> BBB –> hypothalamus (high central ghrelin levels) –> down-regulate leptin –> appetite increased
AKA hunger signal pathway

Question 4

What is the non-homeostatic regulation of energy intake?

Answer 4

Hedonic or reward-based regulation can override the homeostatic pathway during periods of relative energy abundance by increasing the desire for foods that are highly palatable
- cravings
- availability of food
- taste/ smell

Dopamine neurons are involved in the ‘wanting’ of foods and in response to palatable foods

Question 5

Describe the homeostatic regulation of appetite

Answer 5

Appetite control centre –> Hypothalamus (ARC)
2 neurons involved

NPY/AgRP:
- OREXIGENIC –> stimulate appetite and food intake
- coming from adipose tissue or the gastrointestinal system

• In fasting conditions –> NPY/AgRP stimulated and co-released (released separately) –> AgRP blocks alpha MSH on MC4 receptor –> NPY stimulates NPY receptors to increase EI (energy intake)
• NPY/AgRP also can directly inhibit POMC –> preventing appetite inhibition

POMC/CART:
- ANOREXIGENIC –> inhibit appetite and food intake

• After food intake –> (activated) POMC cleaved to alpha MSH which is released from the neuron and binds to MC3/MC4 receptor
• Causes a decrease in food intake
• Potential mediators include BDNF, CRH, and TRH
• Disruption of MC4 receptor can lead to obesity –> signal to inhibit appetite doesn’t work leading to appetite not being reduced/continuing to eat

Both neurons sensitive to leptin, insulin, ghrelin and PYY, glucose, fatty acids and amino acids

Question 6

What is the action of POMC/CART neurons?

Answer 6

POMC/CART:
- ANOREXIGENIC –> inhibit appetite and food intake

• After food intake –> POMC cleaved to alpha MSH which is released from the neuron and binds to MC3/MC4 receptor
• Causes a decrease in food intake
• Potential mediators include BDNF, CRH, and TRH
• Disruption or deficiency of MC4 receptor can lead to obesity

Question 7

What is the action of NPY/AgRP?

Answer 7

In fasting conditions:
- OREXOGENIC –> stimulate appetite and hunger signals

• Blocks alpah-MSH binding to MC4 receptor (AgRP)
• NPY stimulates the NPY receptor to increase energy intake
• Can inhibit POMC/CART action
• Increase appetite

Question 8

What is the median eminence?

Answer 8

Semi-permeable blood brains barriers which signals pass through to go to ARC

Question 9

What happens in the brainstem?

Answer 9

2nd region of homeostatic regulation after hypothalamus
Info from the periphery feeds into the brainstem and onto the HT
The Vagus nerve forms a link between the gut and brainstem (both afferent and efferent signals)

Question 10

What hormones in the gastrointestinal tract are involved in appetite regulation?

Answer 10

Ghrelin –> secreted on an empty stomach
GLP-1 –> influences pancreatic hormone release and glycaemic homesostasis
PYY and GLP1 –> released in lower intestine, release caused by nutrient stimulation and reflexes from upper intestine
CCK, PYY and GLP-1 –> from intestinal L-cells have a decreased peripheral effect on food intake

Question 11

How is ghrelin involved in appetite control?

Answer 11

• Secreted in the stomach
• Orexigenic
• Recognized by the vagus nerve and can bind to NPYAgRP receptors to activate the neuron.
• ‘Meal initiator’ –> levels raise before meals and decrease after
• Increases during a fast
• Stimulates appetite in lean and obese humans

Acts via the vagus nerve, or NPYAgRP activation

Question 12

How is CCK involved in appetite control?

Answer 12

• Levels rise in blood within 15 minutes of the start of the meal
• Released from intestinal cells
• Signals through the vagus nerve
• Peripherally administered CCK reduces meal size and duration in rodents and humans
• Activates POMC/CART
• Releases aMSH, binding to MC4 receptor
• Signalling satiety

Question 13

How is insulin involved in appetite control

Answer 13

Binding to receptors on POMC/CART and NPY/AgRP

Question 14

How does PYY decrease hunger?

Answer 14

Binds to an inhibitory receptor on NPY neurons

Question 15

How is leptin involved in appetite control?

Answer 15

• Levels reflect adipose tissue reserves
• Aim to decrease appetite and food intake
• Leptin resistance is a feature of obesity
• Leptin modulates hypothalamic response to short term energy signals
• Excites POMC/CART neurons
• Inhibits NPY neurons

Question 16

Describe the dysregulated hypothalamic pathway in obesity

Answer 16

Obesity is associated with chronic low grade inflammation
Stress in endoplasmic reticulum in HT causes leptin and insulin resistance
The inflammatory response causes the spontaneous firing of NPR/AgRP neurons –> hyperphagia

Question 17

What is the corticolimbic system?

Answer 17

Non-homeostatic regulation of appetite
- modulated by non-homeostatic factors such as reward, taste etc
- environmental cues can dominate homeostatic regulation

Group of hormones influenced by NHROE

Question 18

What is the Hedonic system?

Answer 18

The ventral tegmental area involved –> dopamine
Fasting/ low blood glucose activates lateral hypothalamus which excite dopamine neurons in the ventral tegmental area
Causes drive for food reward