Week 7-Appetite Flashcards
What is the Model of Appetite Control adapted from Higgs et al., 2017)
The environment + signals from gastro-intestinal (GI) tract relating to ingestion of food affects:
-Cognitive control (Prefrontal cortex, Hippocampus)
-Homeostasis (Hypothalamus)
-Reward - liking and wanting (Dopamine and opioid system)
Define Homeostasis
The ability to maintain a relatively stable internal state
Define metabolism
The process by which your body converts what you eat and drink into energy
Define Hunger
The drive to consume, elicits a behavioural response (eating) to a biological need
Define Satiation
Processes during a meal that generate negative feedback leading to its termination (within-meal inhibition)
Define Satiety
The end state of satisfaction. The further suppression of the drive to consume and post-meal intake (between-meal inhibition)
Define peripheral appetite control
Includes motor functions of the stomach (e.g., rate of emptying) and release of peptides and hormones from the gut and fat tissue
Define Central appetite control
Brain and central nervous system
What are the Negative feedback systems and Energy Balance?
NF: Feedback from changes in one direction elicit compensatory changes in the opposite direction. The act to maintain homeostasis - a stable environment.
EB: Energy Intake (EI) minus energy expenditure (EE).
In an ideal homeostatic energy system an organisms energy intake should equal energy expenditure.
What is the Homeostatic control of energy?
-A biological need to maintain the body’s energy stores
Depletion of energy stores –> drive to eat
Repletion of energy stores –> negative feedback to terminate eating
-Co-ordinated by the hypothalamus
-Harrold et al. (2012) + Berthoud et al. (2017)
How is the homeostatic control of energy asymmetric?
-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 easily than losing weight
-“Eat more” command is dominant over the “Stop eating” command
-Harrold et al. (2012) + Berthoud (2004)
What hormones starts a meal?
Ghrelin: A peptide hormone released by the stomach
-High conc. during breakfast, lunch and dinner then massive drop but levels off after 8pm
What ends a meal?
Gastric Distension which is a potent satiety signal that terminates intake and promotes initial post-meal satiety
-Stretch-receptors signal gastric distension
What is Duodenal’s brake?
CCK’s (Cholecystokinin) response to fat in the duodenum
Decreases the rate of gastric emptying
Satiation and early satiety
What is Ileal Brake?
Occurs further down the small intestine than Duodenal Brake
GLP-1 (Glucagon-like-peptide-1)
Post-meal satiation and reduced hunger at the next meal
What is leptin?
-Plays a long term role in the controlling of appetite and is produced by the adipose tissue (the body’s fat stores) when full
-It results in reduced food intake
-It’s a long term (“tonic”) signal
-Mice with genetic obesity (ob/ob) cannot produce leptin because they are born without the required gene code
What evidence is there that people with obesity have a weaker regulatory control?
-Weaker gastric distension (enlargement of stomach to signal satiety) (Geliebter, 1988)
-Blunted satiety hormone response to eating (PYY, GLP-1) (Lean & Maklova, 2016)
-Rare cases of human obesity where leptin cannot be produced due to gene defect
-However, most people with obesity do not possess a leptin deficiency. In fact, they produce excess leptin. Is obesity therefore due to leptin insensitivity or leptin resistance?
What new drug treatment has been used to cause weight loss?
-Semaglutide aka Wegovy is a GLP-1 receptor agonist
-It works by suppressing appetite and increasing feelings of fullness
-It’s associated with sustained, clinically relevant reductions in body weight
How is the CNS involved in appetite control?
-CNS regions receive signals from the body (e.g., gut, liver)
-The receptors within the CNS can 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
Which 2 Lower CNS structures are involved in appetite regulation and how?
- Vagal nerve: Afferent (inwards/towards) fibres from gastrointestinal tract and liver –> brainstem
- Brainstem (Hind Brain): Relays afferent vagal signals associated with eating to the hypothalamus
- Nucleus Tractus Solitarius - NTS
- Area Postrema - AP (adjacent to NTS)
What are the 4 key hypothalamic sites in the Higher CNS structures involved in appetite regulation? (Harrold et al., 2012)
- Arcuate Nucleus (ARC)
- Ventro-Medial Hypothalamus (VMH)
- Lateral Hypothalamus (LH)
- Paraventricular nucleus (PVN)
What does the ARC do?
-It contains functionally discrete populations of neurones:
- Orexigenic (stimulates food intake)
-Neuropeptide Y (NPY)
-Agouti-related peptide (AGRP) - Anorexigenic (inhibits food intake):
-Pro-opiomealonocortin (POMC)
-Cocaine and amphetamine-regulated transcript (CART)
-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
What Mechanisms create Satiety in the CNS?
-5-HT aka Serotonin is 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 is needed as risk of heart problems)
(Harrold et al., 2012)
What reasons do we enjoy eating?
-Eating for pleasure (to feel better)
-Eating to feel better (takes something negative away)
-Cues associated with the intake of tasty food (e.g., the sight and smell of food) acquire strong motivational properties and become highly wanted
-This is because eating is highly rewarding and reinforcing
What is 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 (i.e., reduced ability and motivation to do as dopamine mediates this)
-It’s argued that the apparent loss of motivation to eat is due to loss of reward or hedonic (pleasure) consequences - that are normally mediated by dopamine
What evidence suggests that the Anhedonia theory is wrong?
- Dopamine blockade prevents animals from attending to food, and working to obtain it - but this reflects motor incapacity NOT a 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 (Berridge, 1996) If something is pleasurable, shouldn’t rats eat more of it?
What is Berridge’s (1996) theory of food reward?
-Food reward contains distinguishable psychological components that are controlled by separate neurobiological systems
-The key distinction is between processes associated with affective vs motivational consequences of consuming food
-Core processes of LIKING and WANTING (Anhedonia theory just assumes reward is pleasure)
Define Liking
Liking represents the pleasure or affective aspects of food. Liking may activate, but does not require wanting (Berridge & Robinson, 2003)
-Explicit=”This food tastes really good!”
-“It’s nice, but it doesn’t grab me” (may like chocolate but may not want to eat it in the morning)
Define Wanting
Wanting is the motivational component also known as “incentive salience” (Berridge et al., 2009). Wanting without liking adds the compulsive element to eating
-Implicit=”I just have to have it, I don’t know why.”
-“Why do I keep eating this?”
What evidence suggests dopamine is not required for liking? (Berridge, 1996)
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
-Chemical lesions are why we can’t do it in humans (so we do it on rats)
-Rats react to taste normally (reacts hedonically)
What does dopamine do if not the “pleasure neurotransmitter”?
Dopamine plays a role in:
-Recognising motivationally important stimuli
-Energising 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
What mediates liking?
-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)
-Evidence for a specific role for opioids in liking (but NOT wanting)
What is cue reactivity?
-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 (drawn to food)
-Physiological changes (e.g., increased salivation)
-Food-seeking behaviours (reminded of a tasty treat means people may go out to get it despite not being hungry/actually needing it)
Define food craving
An intense desire which is directed towards a particular food, drink or taste (Hill, 2007)
-Top 10 most “problematic foods”=chocolate, ice cream, french fries, pizza, cookie, chips, cake, popcorn (buttered), cheeseburger, muffin (Schulte et al., 2016)
-People typically crave energy dense foods with high fat
What happens in our brains when we are craving chocolate? (Rolls & McCabe, 2007)
-Chocolate cravers vs non-cravers (Half participants habitually craved chocolate, the other half didn’t)
-Sight and flavour of chocolate, plus their combination
-fMRI found greater activation in medial OFC and ventral striatum in cravers (these are key brain areas involved in reward)
What is the link between Cue reactivity and obesity?
-Exposure to sight and smell of pizza increased desire to eat and salivary response (getting ready to eat) in participants with obesity relative to participants who were healthy weight (Ferriday & Brunstrom, 2011) –> 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). Because when hungry everyone has an attentional bias to food
What is the Neural evidence for differences in cue reactivity by weight status? (Carnell et al., 2012)
Rothemund et al (2007):
-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 1.5h
-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)
What is the Cognitive control of appetite?
-Without higher level control/executive control, we would be slaves to our reward system (Our reward system has a constant drive and want to consume food - what would happen if we were slaves to it)
-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 & Slice, 2013 who did an fMRI)
How is appetite influenced by cognitive control and the brain?
Cognitive:
-Goals and values (vegan, vegetarian)
-Expectations (taste of food)
-Inhibitory control (i.e., self-control)
-Memories
Brain:
-Involvement of ventromedial-prefrontal cortex (vmPFC) and network that includes dorsolateral prefrontal cortex (dIPFC).
-Obesity is characterised by lower gray matter volume in brain areas important for executive function (suggests brain areas are not working as well as they could do)
-Genetic vulnerability to higher body weight is expressed in brain areas important for cognitive function
García-García et al. (2019). International Journal of Obesity, 43, 943–951.
Higgs et al. (2017). Journal of Psychopharmacology, 31(11), 1460–1474
Vainik et al. (2018). Proceedings of the National Academy of Sciences 115(37), 9312-9317
What evidence is there that Cognitive control increases during satiation?
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), (seen by an fMRI done by Nutr (2015)
→ “top down” cognitive influence on satiation.
Who is patient R.H. (Rozin et al., 1998) and how does it show evidence for recent eating?
-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 was 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).
-Stretch receptor still intact but couldn’t link that to their eating due to damage in medial temporal lobes
