Hunger/Eating [Week 3, Week 4]

Be able to concisely explain: hunger, eating, homeostasis, absorption, hormone.

Hunger: the driver/motivator to eat → eating: the behaviour of ingesting food for satiation and energy → homeostasis: the body’s tendency to maintain an equilibrium → absorption: the process by which nutrients from digested food are taken to the bloodstream, especially in the small intestine → hormone: a substance produced and released by the endocrine glands which travels through the bloodstream to target tissues, where it exerts specific physiological effects

What is the brain’s preferred energy molecule, and where does it get this energy from?

Glucose: the brain prioritises glucose usage, even while fasting → it obtains this energy from circulating blood glucose → when carbs are difested, the GI tract breaks it down to glucose

Compare and contrast the glucostatic and lipostatic set-point theories of feeding behaviour. How do they supposedly work together to maintain stable energy levels? Does our body adhere to a set-point idea?

The Two Main Theories of Hunger: Homeostatic and Hedonic → Homeostatic Feeding/Set Point Theories: where hunger and eating are driven by glucostatic (body aims to maintain blood glucose at a set-point when blood glucose drops, meal initiation when blood glucose rises, meal termination: major flaw: doesn’t explain diabetes) and lipostatic (body aims to maintain body fat % at a set-point when body fat drops, eat high cal foods to replenish reserves when body fat rises, reduce high cal foods to maintain set reserves, major flaw: doesn’t explain obesity) homeostasis → Hedonic Feeding/Positive-Incentive Theories: where hunger/eating are driven by multiple factors (body state, nutrient balance, pleasure, learning, environment, etc - a better explanation of eating disorders

Be familiar with these hypothalamic nuclei, in terms of being able to locate them in cross-section and explain their role in feeding behaviour: ventromedial hypothalamus (VMH), lateral hypothalamus (LH), arcuate nucleus, and paraventricular nucleus (PVN). Understand the basic circuitry of the arcuate nucleus and what states & behaviours (e.g. hunger/satiety or feeding/cessation of feeding) are believed to be triggered by which cells, and in response to what signals.

VMH: lesions to this area cause hyperphagia, so is associated with satiety and body weight regulation → LH: lesions to this area cause aphasia (lack of eating) and adipsia (lack of drinking), so is associated with initiating hunger and food seeking behaviour → AN: contains neurons that regulate hunger and satiety, where NPY neurons stimulate appetite and reduce metabolism, and POMC neurons inhibit appetite and promote metabolism → PVN: involved in integrating signals for feedings/energy balance, receiving inputs from both LH and AN

What physiological mechanisms contribute towards the feeling of hunger and the promotion of eating? Start in the periphery and work your way to the brain - be specific at all levels.

Ghrelin: hormone produced by stomach, increases during fasting, stimulates hunger by signalling the hypothalamus → Low blood glucose/fatty acids: detected by glucodetectors and lipodetectors in liver and brainstem, signal the hypothalamus to initiate eating → vagus nerve: transmits signals from the stomach and intestines to the brain about nutrient status → hypothalamus (LH and AN) integrates signals to generate the sensation of hunger

What physiological mechanisms contribute towards the feeling of satiety and the cessation of food seeking/ingestion? Start in the periphery and work your way to the brain - be specific at all levels.

Insulin: hormone released by the pancrease in response to high blood glucose, signals satiety → PYY3-3tt and CCK: hormones released by the intestines post-meal, signals to the hypothalamus to curb appetite → Leptin: hormone released by adipose tissue, indicates sufficient energy stores to the hypothalamus, reduces hunger → Hypothalamus (VMH, AN, PVN) integrate satiety signals, stops eating

What if a person’s body made defective leptin receptors, such that leptin molecules could not properly bind – how might this affect hunger and eating in that person? Repeat the question with ghrelin receptors, PYY3–36 receptors, CCK receptors and insulin receptors.

Leptin: a hormone that signals about fat reserves, where leptin levels decline when fat reserves decrease, causing you to save energy by eating more and moving less: defective leptin receptors would prevent proper signalling of energy reserves (inability to recognise that the body has sufficient fat reserves), leading to overeating, and obesity → Ghrelin: a hormone that stimulates hunger by signalling to the hypothalamus, which increases during fasting: defective ghrelin receptors could result in reduced hunger signalling, meaning undereating or failure to initiate meals → PYY3-36: a gut hormone released by the intestines after a meal that acts on brain centres to decrease appetite (satiety signal): defective receptors would impair satiety signalling, leading to overconsumption → CCK: a satiety hormone that signals fillness to the brain and slows the rate at which the stomach empties it’s content into the small intestine: defective receptors might cause diminished short term satiety, leading to overconsumption → Insulin: a hormone produced by the pancreas that allows glucose in the bloodstream to enter muscle, fat, and liver cells: defective receptors would impair glucose uptake, leading to elevated blood glucose levels and persistent hunger

Explain, using information presented in class, why alcohol, marijuana and cocaine/amphetamines exert their specific effects on feeding behaviour.

Alcohol: depolarises NPY neurons in the AN, increases hunger and food consumption → Marijuana: activated endocannaboid receptors, which promote appetite (particularly for palatable foods) → Amphetamines: typically suppress appetite by increasing dopamine levels, associated with reward/pleasure thus reducing drive to eat

Understand the difficulty in designing diet drugs, due to system ‘cross-talk’. Use GOAT inhibitors as an example.

Circuitry and signals for function X are often integrated with circuitry/signals for functions Y and Z etc → anatomical and physiological cross talk → ghrelin inhibitors → ‘GOAT’ inhibitors → GOAT is the enzyme that makes ghrelin active, so by inhibiting GOAT you inhibit grhelin which inhibits appetite so decreased feeding = decreased body mass → however ghrelin also does a bunch of other stuff so is it worth it? (eg. reward behaviour, inflammation, goal motivation

Describe the three phases of insulin release. How can insulin condition hunger?

3 Phases of Insulin Release: Cephalic (conditioned release in anticipation of food), Digestive Phase (stimulation of insulin release by food in the GI tract), Absorptive Phase (insulin release triggered by the detection of glucose in the bloodstream by glucodetectors in the liver)

Understand the bidirectional links between the lateral hypothalamus and the ‘reward’ system. Explain why LH activity might promote reinforcement of feeding (Punishment? Reward?), and why VTA activity might promote feeding (Punishment? Reward?).

The LH interacts bidirectionally with the VTA, as LH activity promotes feeding by reinforcing pleasure/reward associated with eating, and VTA activity stimulates dopamine release which enhances motivation to seek and consume food → positive feedback loop that reinforces feeding behaviour

Why do we crave things such as chocolate cake and pizza, but not things such as raw silverbeet? Using just knowledge from PSYC317, give an answer based on neuroscience.

Humans tend to crave calorically dense food (high sugar, high fat), because these foods activate dopamine pathways in the brain which are associated with pleasure and reward → calorically dense foods often provide a quick source of glucose, which the brain loves, and are highly palatable, which reinforces consumption through the brain’s reward circuits (LH, VTA)

“If someone is trying to quit junk food and eat only healthy fruit, vegetables and proteins, they face a constant battle with contextual reinforcement.” Explain this statement. Try to come up with your own examples.

Contextual Reinforcement: where context clues (environmental/social factors, eg. advertisement, availability, etc) reinforce a behaviour → even if someone is trying hard to quit junk food, contextual reinforcement for junk food consumption (which is very common in the modern world, consider the ubiquitous presence of McDonalds and the price of a homecooked healthy meal vs a Big Mac) makes it difficult to avoid junk food

“We are evolutionarily pre-disposed towards weight gain.” Explain this statement.

Refers to the idea that throughout history, the ability to store energy as fat was beneficial to survival in order to persevere through famine → the ‘thrifty genotype’ stores more fat than others, which was advantageous during the relatively common periods of food scarcity/insecurity

What is obesity? Provide a definition. How has the definition changed?

Obesity: an excessive accumulation of body fat, BMI > 30 → nowadays BMI is not preferred, as waist circumfrence and visceral fat distribution are also health metrics better correlated with obesity-related health risks

Differentiate Type I and Type II diabetes. Which one relates more towards the topic of obesity and bariatrics? Briefly explain.

Type 1 Diabetes: Insulin dependent diabetes, an autoimmune condition where insulin producing cells in the pancreas are destroyed, leading to little/no insulin production, requires insulin supplementation to manage blood glucose → Type 2 Diabetes: Insulin resistence, a condition where insulin production is insufficient/insulin receptors are resistant, leading to elevated blood glucose levels, closely related to obesity, often treated with lifestyle changes with medication as a secondary resort

Describe evidence covered in class of genetic/epigenetic factors that may contribute towards obesity. In particular, be familiar with the studies by Plagemann et al. and Huypens et al. (Stick only to what was said in the lecture – no need for more detail)

Plagemann et al: found that overfeeding rats early in life led to methylation changes in genes related to metabolism, correlating to obesity-related phenotypes later in life (heritable - these tags follow generations after, meaning what you do in your life may affect your offspring) → Huyphens et al: demonstrated that feeding a mouse a high fat diet results in obesity AND that these metabolic changes were passed down to offspring via epigenetic modifications in the sperm and eggs

The global human population has gained weight rather suddenly (in the grand scheme of human history). Is it due to our sedentary lifestyles? What conclusions can we draw from McCloskey et al.’s recent (2025) study, in this regard?

Increased availability of highly processed, calorically dense foods → decreased physical activity (but not as much as you’d think! In economically developed countries, people tend to burn more calories even when activity levels are the same, implying sedentary lifestyle in developed countries does not actually contribute majorly to weight gain) → portion sizes have increased a lot since the 80s

What is the Portion Size Effect? What are the theoretical ways in which portion size alters food intake?

Portion Size Effect: the tendency for people to eat more when offered larger portions of food, regardless of whether they are actually hungry

Is the effect of portion size on food consumption mediated by genetic, acquired (learned) or contextual (situational factors)? Briefly describe the evidence presented in the lecture on these points.

Portions act as visual cues that signal how much we should ingest → portions alter bite size and frequency, we adapt our eating behaviours to our contexts → we come to expect larger portions, so it’s acquired/learned also → some theories also state that larger portions present a visual reward

What other dietary change has been linked to obesity? Can this be linked to effort? What did Barrett et al. (2025) find with regard to effort and food consumption in rodents?

Ease of access → requiring rodents to nose poke in order to access high-fat diet reduces calorie intake, blocks the development of obesity → adding friction and making ‘fattening’ foods less easily available can decrease obesity

Briefly explain the ‘gut microbiome’ and how it relates to our behaviour.

Gut microbiome: the microbiota living in the digestive tract → imbalances in the gut microbiome can lead to inflammation, potentially the production of proinflammatory cytokines which can cross the BBB, which can contribute to mood, cognition, and behaviour

Understand the link between diet and inflammation in the hypothalamus, and its effect on appetite/eating.

High fat diets can induce chronic inflammation, including in the hypothalamus (responsible for hunger/satiety) → hypothalamus inflammation disrupts normal signalling pathways that regulate appetite, leading to increased food intake/further weight gain

Understand the emerging link between diet and sleep. What did Titos et al. find in mice and flies? What did Brandão et al., 2023 find in humans?

Titos et al.: dietary proteins can make flies and mice less arousable from sleep, indicating a relationship between diet and sleep quality → Brandao et al.: diets high in junk food associated with poor sleep quality in humans, suggests that the diet can significantly influence sleep patterns and quality, further affecting overall health

Be able to explain the “drug basics” terms presented in lecture (e.g., drug, route of administration, agonist) and concisely describe orlistat (Xenical™) using these drug terms.

Drug: an exogenous chemical that exerts a physiological effect on the body (orlistat is a drug that affects fat absorption) → route of administration: the way a drug is introduced into the body, ie: oral ingestion/inhalation/injection (orlistat is taken orally) → absorption: the process by which a drug enters the bloodstream after administration (orlistat works in the GI tract, so it is minimally absorbed into the bloodstream) → mechanism of action: the specific biochemical interaction through which a drug produces its effect (orlistat works by inhibiting pancreatic lipase, which is an enzyme necessary for fat breakdown, which means orlistat reduces fat absorption) → agonist: a drug that binds to a receptor and activates it → antagonist: a drug that binds to a receptor but does not activate → inhibitor: a drug that binds to a functional protein, and reduces/stops it’s activity (orlistat acts as a lipase inhibitor)

Describe two potential drug targets that – in theory – should reduce hunger and therefore eating. (Do they work in practice?)

Leptin Receptor Agonists: Leptin signals satiety, so if you activate the receptor, hunger should wane, however, many obese patients are leptin-resistant → CB1 Receptor Antagonists: cannaboid receptor type 1 is involved in regulating appetite, so antagonising the receptor can reduce hunger, however, may cause severe anxiety/depression related side effects

Be familiar with the three main types of bariatric surgery and how they each cause weight loss. What are some of the main issues with bariatric surgery in general? Consider things such as risks, efficacy and applicability.

1) Restrictive (eg. gastric band): physically limit the stomach → 2) Malabsorptive (eg. duodenal switch): reroute intestines, reduce nutrient absorption → 3) Combination (eg. gastric bypass): combines both types → Issues: surgical complications, malnourishment, potential weight regain depending on patient lifestyle, nausea/vomiting, not generalisable to all obese patients

Which of these techniques do you think holds the most promise for long-term weight loss maintenance: DBS or faecal transplantation? Why?

Deep Brain Stimulation: implant electrodes into the brain to regulate neural activity → Faecal Transplantation: a healthy donor’s gut microbiome is transplantd into a recipient, this may improve gut health, may target some root causes of obesity (eg. gut flora imbalance), lower risk

How could government policy be shaped to promote healthy eating? Come up with your own strategy, emphasising how reinforcement and reward learning can be harnessed.

Sugar/Fat Tax, advertising regulations on junk food, nutrition education, reinforcement reward-based strategies

How could an individual promote healthy eating in their own life or the lives of their peer group? Come up with your own strategy, emphasising how reinforcement and reward learning can be harnessed.

Positive reinforcement, habit formation, add friction, social influence

What is conditioned taste aversion? Briefly describe the study by Zimmerman et al. (2025), including the circuits they identified as being involved in this phenomenon.

Where an animal learns to avoid a particular taste/smell after experiencing it in association with illness/discomfort (eg. food poisoning)

Know the statistics mentioned in the article. What % of the U.S. population is anorexia nervosa thought to affect? Could it be higher? Are there sex differences? In what % of cases is the disease fatal? How does this % compare with other conditions mentioned in the article? In statistical terms, how effective is treatment?

Just under 1%, but could be higher as many cases go undiagnosed → predominately manifests in girls → 10% highest mortality rate, highest of any psychiatric condition after substance abuse, on par with childhood leukemia → with treatment, half of adolescents recover and 20-30% are helped

Present an overall picture of the prevailing “stereotypical” view of anorexia nervosa, as described in the article.

Predominately affects girls, motivated by thinness/beauty culture, involves ‘extreme willpower’ to overcome the urge to eat, occurs as a response to unloving/controlling/abusive parents

What % the risk of developing anorexia is ascribed to genes, according to the article? How has this been determined?

50-60%

What is the argument that labelling a condition as “biological” rather than cultural or societal is dangerous? What is the counterpoint offered?

Arguments for it being dangerous: may cause patients to give up (gentic determinism), might cause us to be complacent in dealing with the socio-cultural factors (thin-is-in culture) → argument against: might reduce stigma or shame, moves blame away from perceived familial failures, should not imply recovery is impossible, may open the door to new treatments and a better understanding of the disorder’s origin

Briefly describe Zeltser’s study in mice, then revisit the question above ↑. Should anorexia nervosa be framed as something that’s driven by biology, the environment, or both? (Could you add situation to this also?)

Studied mice with a genetic variant linked to anorexia in humans → restricted the mices’ caloric intake by 20-30%, induced stress via isolation → anorexic genetic mice stopped eating, indicates biological aspect → anorexia is driven by interplay between trait and state, should be framed as a complex/multifaceted disorder

Also describe the studies (genetic, pharmacological) that informed Zeltser’s opinion that anorexia nervosa was due to more than only mental control.

Olanzapine (antipsychotic) typically causes profound weight gain → had no effect on people with anorexia → suggests it is not just ‘mental control’ → networks look similar to OCD and addiction

‘This doesn't look like any other psychiatric disorder,’” Bulik says. “It might be the inverse of obesity—these people might be genetically predisposed to low BMI.” Explain this statement, referencing the results from Cynthia Bulik’s lab.

Genetic studies suggest AN’s heritability rate is on par with obesity and depression → 50-60% heritability rate, suggests DNA is highly involved → there are 8 significant genomic regions and other patterns of genetic associations, tracking with results of studies of other psychiatric illnesses (OCD and depression) → ALSO overlapped with DNA controlling BMI, lipids, and other metabolic traits → theorised that it might be the inverse of obesity, in that some people are genetically predisposed to low BMI → one 2019 study showed that the BMI of people later diagnosed with anorexia began to diverge from a control group before they started kindergarten

Describe Walter Kaye’s findings on brain signalling in reward pathways in people with/without anorexia nervosa, plus their self-reported state. What conclusion does Kaye reach?

The circuitry of the brain’s reward system behaves differently in Anorexia sufferers and those recovered → MRI scans show that the dorsal striatum (associated with habit formation) was used when selecting foods, which is different to people without eating disorders → suggests that as people repeatedly restrict eating, the behaviour moves to a different brain region and becomes less amenable to change, possibly explaining why recovered patients may relapse → When offered food (sugar water) after 16 hours of fasting, controls had their reward and motivation circuits light up, but people with AN had much less activity → ‘they could identify being hungry but couldn’t convert that into a desire to eat’, and experienced heightened anxiety and inhibition, along with diminished reward signalling in their brain → suggests they may ‘miscode food as risky rather than rewarding’ → some patients experience an ‘abberant reward’ or ‘starvation high’ → might be a result of the starvation but also might predate the disorder

What is Family-Based Treatment and how effective is it?

FBT → has parents sit down with children and require them to eat → about 50% of people who use FBT as adolescents and about 70% of people who try it early into the disease find it to be effective