Appetite

Question 1

Homeostasis

Answer 1

The ability to maintain a relatively stable internal state.

Question 2

metabolism

Answer 2

The process by which your body converts what you eat and drink into energy

Question 3

hunger

Answer 3

The drive to consume, elicits a behavioural response (eating) to a biological need.

Question 4

satiation

Answer 4

Processes during a meal that generate negative feedback leading to its termination (within-meal inhibition).

Question 5

satiety

Answer 5

The end state of satisfaction. The further suppression of the drive to consume and post-meal intake (between-meal inhibition).

Question 6

peripheral appetite control

Answer 6

Includes motor functions of the stomach (e.g. rate of emptying) and release of peptides and hormones from the gut and fat tissue.

Question 7

central appetite control

Answer 7

Brain and central nervous system.

Question 8

homeostasis and energy balance

Answer 8

• Negative feedback systems:
• Feedback from changes in one direction elicit compensatory changes in the opposite direction.
• Act to maintain homeostasis – a stable environment.
• Energy balance (EB):
• Energy intake (EI) minus energy expenditure (EE).
• In an ideal homeostatic energy system an organisms energy intake should equal energy expenditure.

Question 9

homeostatic control of energy

Answer 9

• A biological need to maintain the body’s energy stores.
• Depletion of energy stores → drive to eat.
• Repletion of energy stores → negative feedback signals to terminate eating.
  Co-ordinated by the hypothalamus.

Question 10

asymmetry of homeostatic control

Answer 10

• Defends well against energy deficit. However, defence against energy excess is weaker.
• → More sensitive to under-eating than over-eating.
• → We can gain weight more than easily than losing weight.
  “Eat more” command is dominant over the “Stop eating” command.

Question 11

what starts a meal

Answer 11

• Ghrelin: A peptide hormone released by the stomach when energy levels are low
  Prior to meals ghrelin levels begin to arise

Question 12

what ends a meal

Answer 12

Gastric Distension- A potent satiety signal that terminates intake and promotes initial post-meal satiety.

Question 13

the gut food and hormones

Answer 13

• CCK (Cholecystokinin)
• GLP-1 (Glucagon-like peptide-1)
• Duodenal Brake- CCK’s response to fat in the duodenum.
• Decreases rate of gastric emptying
• Satiation and early satiety
• Further down the small intestine…
• Ileal Brake- GLP-1 responds to fat.
  Post-meal satiation and reduced hunger at the next meal

Question 14

long term control- leptin

Answer 14

• Produced by adipose tissue (the body’s fat stores) when ‘full’.
  
  • Lots of our energy is stored as fats- evolutionary advantage
• Reduces food intake.
• Long term (“tonic”) signal.
  Mice with genetic obesity (ob/ob) cannot produce leptin because they are born without required gene code.

Question 15

evidence for weaker regulatory control in people with obesity

Answer 15

• Weaker gastric distention (Geliebter, 1988).
• Blunted satiety hormone response to eating (PYY, GLP-1) (Lean & Malkova, 2016).
• Rare cases of human obesity where leptin cannot be produced due to gene defect.
• However, most people with obesity people do not possess a leptin deficiency. In fact, they produce excess leptin
  → leptin insensitivity or leptin resistance?

Question 16

new drug treatments- fulness

Answer 16

• Semaglutide (Wegovy) is a GLP-1 receptor agonist.
• Works by supressing appetite and increasing feelings of fullness.
  Associated with sustained, clinically relevant reductions in body weight.

Question 17

central nervous system appetite control

Answer 17

• CNS regions receive signals from the body (e.g. gut, liver).
• Receptors within the CNS also detect circulating levels of nutrients.
• Substances, such as glucose, can cross the blood-brain barrier.
  Specific neuronal populations recognise and integrate multiple energy-relevant signals and act in a network to determine energy intake and expenditure.

Question 18

CNS structures involved in appetite regulation- lower

Answer 18

• Vagal Nerve
  
  • Afferent fibres from gastrointestinal tract and liver → brainstem
• Brainstem (Hind Brain)
  
  • Relays afferent vagal signals associated with eating to the hypothalamus. Key sites are:
  • Nucleus Tractus Solitarius - NTS.
  • Area Postrema - AP (adjacent to NTS).

Question 19

CNS structures involved in appetite regulation- higher

Answer 19

• CNS structures involved in appetite regulation- higher
  
  • Hypothalamus
  • Key hypothalamic sites:
  • Arcuate Nucleus (ARC)
  • Ventro-Medial Hypothalamus (VMH).
  • Lateral Hypothalamus (LH).
    Paraventricular Nucleus (PVN).

Question 20

CNS structures involved in appetite regulation- neuronal populations

Answer 20

• The ARC contains functionally discrete populations of neurones:
• The ARC has extensive reciprocal connections with other hypothalamic regions including the PVN, VMH, and LH.
• These regions receive afferent information via the NTS/AP.
• CNS mechanisms: satiety
• 5-HT (Serotonin):
  
  • A key CNS satiety signal in the short-term (“episodic”) regulation of food intake.
  • 5-HT drugs are successfully used as appetite suppressants to treat obesity.
  • The 5-HT drug Lorcaserin was hailed by the media as a “magic bullet” (but caution needed)

Question 21

reward motivated eating

Answer 21

• Eating for pleasure
• Eating to feel better
• Cues associated with the intake of tasty foods (e.g. the sight and smell of food) acquire strong motivational properties and become highly wanted

Question 22

is dopamine the pleasure neurotransmitter?

Answer 22

• The Anhedonia theory (Wise, 1982):
• Dopamine mediates pleasure, based on observation of rat behaviour:
• Disruption of brain dopamine systems lead to failure to eat or drink.
• Dopamine receptor antagonists reduce working for food.
  Argued that apparent loss of motivation to eat is due to loss of reward – or hedonic consequences – that are normally mediated by dopamine.

Question 23

why the anhedonia theory is wrong

Answer 23

• Dopamine blockade prevents animals from attending to food, and working to obtain it – but this reflects motor incapacity not motivational deficit.
• Stimulating dopamine activity can increase responding for food – but doesn’t increase how much is eaten!
  Critical experiments show that dopamine is not required for the experience of pleasure from eating.

Question 24

Berridges theory of food reward

Answer 24

• Food reward contains distinguishable psychological components that are controlled by separate neurobiological systems.
• Key distinction is between processes associated with affective vs. motivational consequences of consuming food.
  → Core processes of Liking and Wanting.

Question 25

liking vs wanting

Answer 25

• Liking represents the pleasure or affective aspect of food. Liking may activate, but does not require, wanting.
  Wanting is the motivational component – also known as “incentive salience”2. Wanting without liking adds the compulsive element to eating.

Question 26

dopamine is not required for liking

Answer 26

• Chemical lesions of brain dopamine systems using 6-hydroxydopamine (6-OHDA)
  
  • Aphagia (rejection of food)
  • Adipsia (absence of thirst)
  • but NORMAL taste reactivity
    Hedonic evaluation of food (“liking”) is therefore independent of dopamine.

Question 27

dopamine and incentive salience

Answer 27

• So, if dopamine is not the ‘pleasure neurotransmitter’, what does it do?
• Dopamine does play a role in:
  
  • Recognizing motivationally important stimuli.
  • Energizing of goal-directed behaviour.
  • Learning of associations between psychological state/experience, environmental stimuli and behaviour.
  • Effort.
    Dopamine thus serves alerting and activating functions related to wanting.

Question 28

what mediates liking

Answer 28

• Natural opioid (opiate-like) chemicals occur in the brain.
• Morphine (opioid agonist) increases food intake.
• Opioid antagonist drugs reduce food intake.
  
  • Naloxone reduced hedonic preference for sweet, high-fat foods in humans (Drewnowski et al. 1992, Physiology & Behavior, 51, 371-9).
    Evidence for a specific role for opioids in liking (but not wanting).

Question 29

obesity and food liking

Answer 29

• Little evidence that individuals with obesity experience greater food liking
  Individuals with obesity work harder to obtain food

Question 30

cue reactivity

Answer 30

• Learned associations between food cues (e.g. the sight and smell of food) and the rewarding consequences of eating.
• These cues elicit conditioned responses such as:
  
  • Increased desire and craving for food.
  • Attentional bias.
  • Physiological changes (e.g. increased salivation)
    Food-seeking behaviours.

Question 31

craving

Answer 31

• Food craving - an intense desire which is directed towards a particular food, drink or taste (Hill, 2007, Proceedings of the Nutrition Society, 66, 277-285).
  Top ten most “problematic foods”: (Schulte et al., 2016, PLoS ONE 10(2): e0117959).

Question 32

what is happening in our brains when we crave chocolate?

Answer 32

• Chocolate cravers vs non-cravers
  
  • Sight and flavour of chocolate, plus their combination
  • fMRI
    Greater activation in medial OFC and ventral striatum in cravers

Question 33

cue reactivity and obesity

Answer 33

• Exposure to sight and smell of pizza increased desire to eat and salivary response in participants who were overweight relative to participants who were healthy weight (Ferriday & Brunstrom, 2011, International Journal of Obesity, 35(1), 142-149).
• → increased motivation to consume food.
  People with obesity showed a greater attentional bias to food images, but only when they were satiated (Castellanos et al., 2009, International Journal of Obesity, 33(9), 1063-1073).

Question 34

neural evidence for differences in cue reactivity by weight status

Answer 34

• Rothemund et al. (2007), NeuroImage, 37, 410-421.
• fMRI study - responses to pictures of high-calorie foods, low-calorie foods, eating-related utensils and neutral images, following abstinence from eating for at least 1.5 h.
• Women with obesity (BMI > 30) - greater activation to high-calorie foods vs. neutral images in the caudate/putamen (reward/motivation), anterior insula (taste, interception, emotion), hippocampus (memory) and parietal cortex (spatial attention).
  In relation to control group of women who were lean (BMI 19–24)

Question 35

cognitive control of appetite

Answer 35

• Without higher level control/executive control, we would be slaves to our reward system.
• But we do not always respond to the presence of food cues by initiating eating. Some individuals are very successful at controlling their food intake.
  An appetitive response to a tasty food may be inhibited if the individual has a long-term goal for health (for empirical support see Yokum & Stice, 2013, International Journal of Obesity, 37(12), 1565-1570).

Question 36

cognitive control of appetite and the brain

Answer 36

• Involvement of ventromedial-prefrontal cortex (vmPFC) and network that includes dorsolateral prefrontal cortex (dlPFC).
• Obesity is characterized by lower gray matter volume in brain areas important for executive control.
  Genetic vulnerability to higher body weight is expressed in brain areas important for cognitive function

Question 37

cognitive control increases during satiation

Answer 37

• Thomas et al (2015):
• 16 healthy participants were scanned on 2 separate test days, before and after eating a meal to satiation or after not eating for 4 h.
• Satiation reduced activity in reward-related brain regions.
• Satiation increased activity in the dorsolateral prefrontal cortex (dlPFC),
  → “top down” cognitive influence on satiation.

Question 38

memory for recent eating- the case of patient RH

Answer 38

• R.H. had bilateral damage to the medial temporal lobes which resulted in severe amnesia.
• He was able to eat multiple meals:
  
  • Ate three meals in a short space of time. Rejected a fourth meal because his “stomach as a little tight”.
  • R.H was unable to remember his recent eating and continued to eat as a result.
    A large number of studies with neurologically intact participants indicate that memories about recent eating episodes are an important determinant of food intake (Higgs, 2005, Physiology & Behavior, 85, 67-72).

Question 39

peripheral appetite signals

Answer 39

• Stomach distension - stretch receptors transmit signals via the vagus (afferents) to the hypothalamus.
  Signals satiation and inhibits food intake.

Question 40

balloon belly (Geliebter, 1988)

Answer 40

• N = 8 (4 with obesity, 4 lean).
• Within-subjects design (6 conditions). Small, standardised breakfast, ingestion of ‘gastric balloon’:
  
  • 0mL inflation
  • 100mL
  • 200mL
  • 400mL
  • 800mL
  • 800mL inflation followed by immediate deflation
• Dependent variable: Intake of liquid meal
  Balloon was passed orally into the stomach of four lean and four participants with obesity before they ingested a liquid lunch meal. The balloon was filled with 0, 200, 400, 600, and 800 ml of water in a random sequence on different days. The balloon was kept inflated during ingestion then deflated and removed. Food intake was significantly reduced (p<0.01) by a balloon volume of ⩾400 ml

Question 41

Geliebter 1988- differences in stomach capacity by body weight

Answer 41

• Inflation of balloon in 100mL steps.
• Participants rated their discomfort as 1 to 10.
• Larger stomach capacity in participants with obesity (relative to participants who were lean).
• In the second study, another balloon was inserted into the stomach of these subjects to estimate stomach capacity. The balloon was gradually filled at the rate of 100 ml/min with 30 sec pauses. The subjects rated their discomfort as 1 to 10, from no discomfort to extreme discomfort. A rating of 10 was the main index for stomach capacity.

Critical analysis
- Study isolated effects of stomach distension on appetite, independent of metabolic effect of nutrient ingestion.
- Strengths included within-subjects design and standardisation of appetite at baseline.
* BUT weight-related differences in gastric capacity, metabolic needs, habitual meal size, mean that standardisation might not have been as effective for group comparisons (Study 2)
- Also…
- Small sample size.
- Naturalistic eating conditions?

Practical implications
- Intragastric balloon as a (temporary) therapeutic device to treat obesity.
* Patient experience
- But potential for serious adverse events, and questionable efficacy compared to other treatment options (Tate & Geliebter, 2017, Advances in Therapy, 34, 1859-1875).

Question 42

Milkshakes and fake saliva- Burger & Slice, 2013

Answer 42

• How to measure neural activity in response to food consumption?
• Practical challenge: eating in the scanner – chocolate milkshake
• Control stimulus? Tasteless solution designed to mimic taste of saliva
• N = 155 healthy-weight adolescents, standardised appetite.
• Measured neural activity in response to anticipated intake and during intake:
  
  • Attentional regions (visual and medial prefrontal cortices).
  • Reward regions (striatum).
  • Gustatory and oral somatosensory regions (e.g., anterior insula, postcentral gyrus, opercula).
• 2-week energy intake estimated (doubly labelled water).
• Energy intake correlated with increased activity in anticipation of palatable food in:
  
  • Visual cortex (visual processing and attention).
  • Frontal operculum (gustatory [taste] cortex).
• No association energy intake and BOLD responses during consumption of palatable food.

Critical analysis
- Provides novel evidence on the associations between brain reward and habitual energy intake (not ‘fat mass’ driving effects as in previous studies of participants with or without obesity).
- Objective measure of energy intake.
- But cross-sectional and observational research:
* Experimental manipulation of energy intake (i.e., change energy intake to examine changes in BOLD signals) necessary to disentangle direction of causality.

Practical implications
- Strengthening cognitive control / inhibition of cue reactivity and reward:
* Computerised tasks training inhibition of automatic motivations toward palatable foods as a potential adjunct to weight loss programs (Lawrence et al., 2015, Appetite, 85, 91-103).

Question 43

the never ending soup bowl- Brunstrom et al., 2012

Answer 43

• Between-subjects design (N = 100).
• 2 (perceived soup volume) x 2 (ingested soup volume).
• Hunger rated immediately after, and +1, 2, 3 hours.

Critical analysis
- Study isolated effects of perceived intake (cognitive influence on satiety) from actual intake
- But…
- No measure of actual food intake.
- Episodic memory manipulation confounded with:
* Pre-meal expectations? Disappointment vs satisfaction with portion.
* Eating rate? Eat faster when perceived smaller portion à weaker satiety response (Wilkinson et al. (2016). PLoS One, 11(2), e0147603).

Practical implications
- Attentive eating versus distracted eating – impact on meal memory and potential to influence later intake:
* Review of evidence (Robinson et al. (2013) American Journal of Clinical Nutrition, 97(4), 728-742).
- Attentive eating advice via a phone app to supplement to weight loss program:
* Robinson et al. (2013). BMC Public Health, 13, 639.

Question 44

manipulating eating rate

Answer 44

• Specific verbal instructions “chew 15 / 40 times per mouthful”
  
  • Impact on satiety hormones (Zhu et al. (2013). British Journal of Nutrition, 110(2), 384-390).
• Instructions + facilitate with spoon size (Andrade et al (2008). Journal of the American Dietetic Association, 108(7), 1186-1191).
  Measure pace and provide real time feedback to increase/decrease speed (Zandian et al.(2012). BMC Public Health, 12, 1-8).

Question 45

universal eating monitor

Answer 45

• Allows covert monitoring of intake (and eating rate) during meal using concealed scales underneath food tray
  (Kissileff et al. (1980). American Journal of Physiology, 238(1), R14-R22).

Question 46

manipulation of oral cavity size

Answer 46

Reduce oral cavity size to reduce bite size and eating rate:
McGee et al. (2012). Obesity, 20(1), 126-133.
A potential intervention- (another example of University of Liverpool research!)

Summary