Brain-body systems for energy balance and response to stress

Question 1

What hormone maintains body weight?

Answer 1

Leptin
Level of leptin in the blood is directly linked to the amount of body fat you have

Question 2

What is the function of ghrelin?

Answer 2

Ghrelin is a hormone produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a “hunger hormone” because it increases the drive to eat

Question 3

What signalling inhibits feeding behaviour?

Answer 3

Low energy reserves establish a motivational state that leads to feeding behaviour - this can either be promoted or inhibited via the hypothalamus

Signalling from fat cells (leptin) and via insulin levels inhibit feeding behaviour

Question 4

What signalling promotes feeding behaviour?

Answer 4

Signalling by cells of the stomach/GI system (ghrelin) when empty promotes feeding behaviour

Mechanoreceptors in GI tract also sense fullness and signal to brain via vagus nerve

Question 5

What is a complication with brain-body system for energy balance?

Answer 5

Not just as simple as signalling for appetite control to maintain energy balance

Need to remember the objective is energy balance so responses will also impact on metabolism of fat and autonomic nervous system actions to prepare for physical activity

Question 6

What is the ARC?

Answer 6

The arcuate nucleus of the hypothalamus

Integrates circulating signals of hunger and satiety reflecting energy stores and nutrient availability

Is a key integrator for hormone signalling input
Projects to other hypothalamic structures and onwards into cortical and limbic circuits

Question 7

What is hedonic hunger?

Answer 7

Hedonic = refers to one’s preoccupation with and the desire to eat foods for the sole purpose of pleasure and in the absence of physical hunger

Question 8

What is the reasoning behind the hedonic regulation of feeding behaviour?

Answer 8

Food as a primary reinforcer activates brain reward circuitry to establish a ‘liking’ for food alongside a ‘wanting’ as behavioural motivators

Dopaminergic signalling from the ventral tegmental area (VTA) to the nucleus accumbens underlies food reward and this ‘hedonic drive’

Question 9

What is the evolutionary reasoning behind hedonic regulation of feeding behaviour?

Answer 9

Powerful motivational mechanisms for seeking and consumption of food arise from evolutionary pressures in the context of general scarcity of this key resource

As a result, overeating in the face of present abundance could be an understandable overshoot inherited from our evolutionary past.

Question 10

What controls hedonic regulation of feeding behaviour?

Answer 10

Mesolimbic system - dopaminergic pathway (reward pathway)

Ventral tegmental area in the midbrain projects to the nucleus accumbens (ventral striatum) causing dopamine levels to rise

The ventral striatum includes the nucleus accumbens and the olfactory tubercle

Question 11

How are the hedonic and homeostatic circuits for regulating feeding and energy balance integrated?

Answer 11

HEDONIC
- Prefrontal cortex
- Nucleus accumbens
- Ventral tegmental area

HOMEOSTATIC
- Lateral hypothalamus
- Arcuate nucleus of hypothalamus

Question 12

What is the role of the PFC in hedonic hunger?

Answer 12

Executive functions
Goal directed behaviour
Information processing
Working memory
Emotional regulation
Retrieval of memory
“Learning” component

Question 13

What is the role of the NAc in hedonic hunger?

Answer 13

Cognitive processing of reward
Motivational salience
Positive reinforcement
Hedonic hotspot or pleasure centre
“Liking” component

Question 14

What is the role of the VTA in hedonic hunger?

Answer 14

Main dopaminergic centre
Reward seeking
Reward prediction
“Wanting” component
Binge/intoxication (addiction)

Question 15

What is the role of the LH in homeostatic hunger?

Answer 15

Integration of information from cortical, extended amygdala and basal forebrain networks
Generation of a highly specified and invigorated behavioural state
Primary orexinergic nucleus

LH also plays a role in hedonic hunger

Question 16

What evidence is there for the role of the lateral hypothalamus in hedonic hunger?

Answer 16

Teitelbaum and Epstein (1962) provided the first evidence that LH was also involved in causing the hedonic impact of palatable food

They found that lesions of LH caused the rats to react with intense aversive reactions, such as disgust-type gapes, to palatable, sweetened milk

Question 17

What is the role of the Arc in homeostatic hunger?

Answer 17

Appetite regulating neurons
Regulation of neuroendocrine secretion
Integration of peripheral signals (leptin, ghrelin, insulin)

Question 18

Explain the model proposed by Volkow et al. (2008) for obesity

Answer 18

Overeating reflects an imbalance between circuits that motivate behaviour (because of their involvement in reward and conditioning) and circuits that control and inhibit pre-potent responses

4 main circuits

1. Reward-saliency
2. Motivation-drive
3. Learning-conditioning
4. Inhibitory control-emotional regulation-executive function

Question 19

What is obesity caused by according to Volkow et al. (2009)?

Answer 19

The ability to resist the urge to eat requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from eating the food and the desire to eat the food

Imaging studies show that obese subjects might have impairments in dopaminergic pathways that regulate neuronal systems associated with reward sensitivity, conditioning and control

It is known that the neuropeptides that regulate energy balance (homeostatic processes) through the hypothalamus also modulate the activity of dopamine cells and their projections into regions involved in the rewarding processes underlying food intake

It is postulated that this could also be a mechanism by which overeating and the resultant resistance to homeostatic signals impairs the function of circuits involved in reward sensitivity, conditioning and cognitive control

Question 20

What did Volkow et al. (2009) consider in his review paper?

Answer 20

Brain reward circuits can be activated by the same hormones that are key for homeostatic regulation

Leptin decreases whereas ghrelin increases reactivity to food stimuli in brain reward areas

In individuals with obesity, central reward circuits responses to food stimuli are blunted, whereas primary somatosensory signalling related to palatability are enhanced

Question 21

What did Farooqi et al. (2007) find?

Answer 21

Leptin which acts in part though leptin receptors in hypothalamus (arcuate nucleus) to decrease food intake, has also been shown to attenuate the response of brain reward regions to food stimuli

Patients with congenital leptin deficiency showed activation of DA mesolimbic targets (NAc and caudate) to visual food stimuli, which was associated with food wanting, even when the subject had just been fed

By contrast, mesolimbic activation did not occur after 1 week of leptin treatment

This was interpreted to suggest that leptin diminished the rewarding responses to food

Question 22

What is oxytocin?

Answer 22

Love hormone
Key for prosocial behaviours and bonding

Question 23

How is oxytocin linked to hypothalamic and hedonic regulation of feeding behaviour?

Answer 23

Recent evidence suggests that it can modulate calorie intake and metabolism

Oxytocin released by hypothalamic neurons when food reward is known to be present and can modulate both hedonic and homeostatic pathways

One other mechanism of action may also be via reduced stress responses via downregulation of the HPA axis

And recent research suggests that oxytocin released into the circulation may re-enter the brain across the blood brain barrier

Question 24

What did Lawson et al. (2017) find regarding the role of oxytocin in energy balance?

Answer 24

A single dose of intranasal oxytocin reduces caloric intake in men, particularly of more palatable foods, and these effects could be increased in men with obesity

Intranasal oxytocin acutely increases the use of fat as a fuel for the body, but effects of oxytocin in promoting energy expenditure have not been demonstrated in humans

Question 25

How does leptin resistance occur?

Answer 25

Leptin resistance is caused by chronically high leptin levels

This can be peripheral - due to inflammation-related effects on the BBB

Or central - via modulation of brain leptin receptors

This creates a positive feedback loop as satiety signalling is increasingly impaired, which can lead to increased consumption of food, and further impairment of satiety signalling

Question 26

What is key in mobilising bodily systems appropriately and rapidly in the event of an acute threat?

Answer 26

Hypothalamus
Endocrine glands
Hormones

Question 27

What are the two primary pathways that are activated in response to an acute stressor?

Answer 27

1. Sympathetic-adrenal-medullary pathway
2. Hypothalamic-pituitary-axis

Question 28

Describe the sympatho-medullary pathway

Answer 28

Acute stressor –> cerebral cortex –> hypothalamus –> sympathetic nervous system –> adrenal medulla –> release adrenaline + noradrenaline –> increased blood pressure and heart rate

Question 29

Describe the hypothalamic pituitary adrenal axis

Answer 29

Acute stressor –> cerebral cortex –> hypothalamus –> Corticotropin releasing factor (CRF) –> pituitary gland –> Adrenocorticotropic hormone (ACTH) –> adrenal cortex –> releases cortisol

Question 30

What happens during activation of the sympathetic adrenal medullary pathway?

Answer 30

The hypothalamus projects via the brainstem and spinal cord to activate sympathetic nervous system
Activation of the adrenal glands and the adrenal medulla specifically is a key component as this causes the production of adrenaline

Question 31

What are the effects of adrenaline?

Answer 31

A circulating hormone (although also a neurotransmitter)

Adrenaline makes your heart beat faster and your lungs breathe more efficiently. It causes the blood vessels to send more blood to the brain and muscles, increases your blood pressure, makes your brain more alert, and raises sugar levels in the blood to give you energy. Your pupils grow larger and you sweat.

Question 32

How does adrenaline work?

Answer 32

Acts in concert with other sympathetic nervous system effects

Unlike most other circulating hormones, adrenaline does not have a direct negative feedback mechanism

In effect, requires absence of the stressor for reduction in levels

Question 33

What parts of the adrenal gland are adrenaline and cortisol released?

Answer 33

Adrenaline = MEDULLA
Cortisol = CORTEX

Question 34

What occurs during HPA axis activation?

Answer 34

Hypothalamic activation triggers the release of corticotropin releasing hormone

This acts on the anterior pituitary gland causing it to release adrenocorticotropic hormone

This triggers the release of cortisol from the adrenal cortex

Question 35

What are the effects of cortisol?

Answer 35

Mainly responsible for two things:
1. Elevation of glucose availability (breakdown of fat and protein)
2. Immune suppression/regulation

Other functions:
Increases blood sugar, increases blood pressure, reduces allergic reactions, slows digestion, raises or lowers serotonergic function

Question 36

What occurs if the two stress response systems are exposed to chronic stressors?

Answer 36

The systems are setup to prepare the body to deal with an immediate and short term threat

Continuous activation of stress response systems can have a range of undesirable systemic and neurological effects

HPA axis dysregulation is associated with major depression and reduced cognitive function - probably occurs due to central reductions in sensitivity to circulating cortisol (as the critical negative feedback system)

Question 37

What is a critical feature of brain systems controlling stress responses?

Answer 37

They require stressor termination and/or negative feedback for effective and healthy operation