Neurobiology Of Appetite Flashcards
How m any pounds do we gain/year
1-2 pounds
Timeline for energy expenditure vs intake
Continuous vs episodic
2 systems that regulate appetite and food intake
Homeostatic (metabolic)
Hedonic (reward system)
What are the two adiposity related (long term) signals for satiety?
Insulin and lepton
What are the 2 nutrient related signals that stimulate satiety?
Glucose and FFAs
What are 2 short term satiety signals that travel through the vagus nerve and spinal nerves
CCK and GLP1
Function of the homeostatic regulatory system
How does it achieve that? (2)
Senses the nutritional and metabolic state of the body to prevent weight loss and maintain fat stores by balancing energy intake with energy expenditure over time - regulates the body’s set point
- stimulates hunger when energy levels are low
- suppresses appetite when energy levels are sufficient
How does the homeostatic system accommodate for growth?
The set point for the amount of energy that you body needs increases as you age and does not seem to stop.
Key areas of the brain involved in homeostatic appetite regulation
Hypothalamus
Dorsal vagal complex (brain stem)
Two parts of the hypothalamus
Accurate nucleus and median eminence
Two types of neurons in the arcuate nucleus and what they do
NPY/AgRP neurons - stimulate appetite
- neuropeptide Y
- Agouti related peptide
POMC/CART neurons - suppress appetite
- pro-opiomelanocortin
Cocaine and amphetamine- regulated transcript
What is the median eminence?
Incomplete blood brain Barrie that samples circulating satiety hormones
What does the dorsal vagal complex contain? (2)
Nucleus of the Tractus Solitarius
- receives input from vagal nerve (afferent nerve impulses)
Area postrema
- incomplete blood brain Barrier that samples circulated satiety hormones
Where does the dorsal vagal complex relay signals?
Hypothalamus
What is the short term orexigenic (hunger) hormone? And where is it from?
Ghrelin - released from stomach
What are the four short term anorexigenic (satiety) hormones and where are they from?
Peptide YY (PYY) - L cells (ileum and colon) Pancreatic Polypeptide (PP) - pancreatic islets of Langerhans - PP cells Glucagon-like peptide - 1 (GLP-1) - co-secreted with PYY from L-cells (ileum and colon) CHolecystokinin (CCK) - I-cells (proximal small intestine)
Satiety
Physical feeling of fullness
Satiation
End of desire to eat after a meal
What neurons would hunger hormones stimulate?
NPY/AgRP
What neurons would satiety stimulate?
POMC and CART
Where are L cells located?
Distal ileum and colon
What is lepton released in proportion to?
Adipose tissue mass
Where is insulin released?
Beta cells in the pancreas
What are the two long term anorexigenic hormones?
Lepton and insulin
Functions of lepton and insulin (2)
Activate POMC/CART neurons and reciprocally inhibit NPY/AgRP neurons
What struggle does the lepton deficiency disorder face?
Lepton deficiency obesity is not very popular, but they have trouble controlling their appetite
What is the hedonic regulation
Reward system - brain mechanism that promotes behaviour that are beneficial for survival and procreation
What does hedonic regulation lead to? By doing what? (2)
Food intake above and beyond homeostatic control/homeostatic override
- conditioning - neutral cues gain incentive such as sight, small and taste
- unconsciously guide executive decision making
Two components of hedonic regulation
Mesolimbic dopamine pathway
Endocannabinoid and opioid receptors
5 things under the control of your hedonic regulation
Money, salt, sugar, fat, sex
What does hedonic regulation exploit?
Opportunities of abundance - we used to compete for food with other species - so we would consume as much as we can when we get the chance to
Conditioning of hedonic regulation?
Dopamine is released when certain things are consumed
Munchies from marijuana goes through what pathway
Encocannabinoid pathway of hedonic regulation
What does hedonic regulation have a heightened response to?
Highly palatable and calorically dense foods
- fat, sugar, salt
Interactions between homeostatic and hedonic systems
Homeostatic hunger enhances food reward - elevated ghrelin and reduced lepton, insulin, and other satiety hormones alter signaling in the reward system of the brain. (After fasting sweetened foods did not get a big drop in dislike)
Other than hedonic and homeostatic regulation, what’s the last regulation that decides to eat or not to eat?
Cognitive regulation
What are three cognitive aspects of food intake?
Self regulation/dieting, social feedback, environmental feedback
How many decisions do we make about when where what with whom and how much to eat everyday?
230, underestimated by 215 decisions
How does marketing tailor to biology and hard wired innate food preferences?
Finding the bliss point to elicit physiological responses that are normal and realistic
Digital images of highly palatable food may
Adversely affect our appetite-regulating neural signalling
3 factors in food that promote satiety?
Fibre, protein, water content
2 effects of dietary fibre on appetite
Subjective appetite reduced by ~5%
Reduced energy intake but ~2.6%
Paleo diet may
Enhance satiety
Hedonic system promotes consumption of palatable, energy dense food in the absence of?
Physiological hunger
When does the homeostatic and hedonic system interact to promote food intake?
Periods of energy insufficiency
In normal subjects, their body weight is tightly regulated despite
Day to day variation in food intake and energy expenditure
What does the body system favour in terms of energy?
Preservation of energy because it has evolved to conserve energy
What do energy signals do? And where does it converge?
Relay info such as the nutritional and energy status of the body and it converges within the CNS
What two factors in humans that can drive excess food intake?
Psychological and emotional factors
Two things in the modern lifestyle that makes obesity easy
Easily available palatable foods and reduced levels of PA
What can result in obesity in rare cases?
Mutations within genes encoding known appetite regulating hormones
What plays a major role in the control of appetite?
Hypothalamus
What allow peripheral circulating factors direct access to the CNS?
Incomplete blood brain barrier at the median eminence of the hypothalamus and area postrema of the brain stem
What hormone is produced in POMC neurons and what do they bind to?
Alpha-melanocyte- stimulating hormone (alpha-MSH) and it binds to melanocortin-4 (MC4R) receptors in the PVN (paraventricular nucleus)
How is the orexigenic effect of NPY mediated?
By stimulation of hypothalamic Y1R and Y5R in addition to local inhibition of POMC neurons in the ARC
Two ways peripheral signals can convert information
Neural pathways via the brain stem and hypothalamus
Incomplete blood brain barrier at the median eminence and rare postrema - gut hormones and adiposity signals can act via the bloodstream to influence signaling of known appetite controlling pathways like NPY ArRP and POMC/CART in the arcuate nucleus.
Signals from higher cortical centres are integrated with?
Peripheral finals within hypothalamic nuclei
3 parts of the dorsal vagal complex
Dorsal motor nucleus, area postrema, nucleus of the tractus solitarius
What does the vagal come from and what does it do?
Afferent from the gut to convey info such as gastric distension, gut hormone levels and fatty acids
Periphery signals have pivotal roles in what?
Transmitting info via afferent vagal fibres to the caudal brainstem or directly to the hypothalamus to modify appetite
Corticolimbic pathways
Reward associated feeding behaviour with the endocannabinoid and opioid receptors
Rimonabant
Endocannabinoid receptor antagonist - used for a treatment for obesity but has unacceptable psuchiatric side-effects resulting in withdrawal of the drug
What’s referred to as the largest endocrine organ in the body?
Gastrointestinal tract
PYY - what is it? How many forms, where is it released?
Peptide tyrosine tyrosine - two circulating forms of it released by L cells in the distal gut
Circulating PYY concentration
Low in the fasted state and rapidly increases following a meal - peak at 1-2 hours and remain elevated for several hours
2 effects of PYY
Anorectic, increases energy expenditure
How does PYY have anorectic effects?
Incomplete blood brain barrier in the median eminence of the hypothalamus, via vagal brainstem hypothalamic pathways, or both.
PP concentration
Circulating PP concentration rise after a meal in proportion to the caloric load
GLP- 1
Where is it secreted?
Glucagon-like peptide-1
Consecrated with PYY from the L cells in the intestine
Circulating GLP-1 levels
Rise after a meal and fall in the fasted state
What does GLP-1 do?
Reduce food intake
Intravenous infusion of GLP-1
Does dependent reduction in food intake in both normal weight and obese subjects
Circulating ghrelin
Increase before meals and fall rapidly after eating
Peripheral administration of ghrelin
Increase c-fos expression in ARC NPY/AgRP neurons
First hormone known to modulate food intake and its plasma half life
CHolecystokinin - few minutes
CCK levels
Rapidly reaches a peak within 15 minutes after a meal
Adiposity signals are involved in
Long-term regulation of energy balance
What modulates food intake on a meal by meal basis?
Gut peptides
Circulating levels of insulin and lepton and what is it responsible for?
Proportional to adipose tissue - long term regulation of energy balance
Insulin concentration
Secreted rapidly after a meal
Central administration of insulin
Suppresses the fasting induced increase in NPY mRNA levels and increases POMC mRNA expression
Where is leptin secreted?
Adipocytes
How does leptin work?
Transported across the BBB by a saturable system and exerts anorectic effect via the ARC - both NPY/AgRP and POMC/CART neurons express leptin receptors but the first one is inhibited and the second is activated to reduce food intake and increase energy expenditure
Given the enormous amount of food eaten, it is remarkable that we
Keep a stable body weight throughout adulthood
Besides the hypothalamus, what other brain areas are in the circuitry of the homeostatic regulator?- 3
Brainstem, basal ganglia, cortico-limbic system
Advertisement in food industry
Use food and pictures of food to neuromarket - esp children because it generates future buyers of brand name products
Does stimuli from the environment have the capacity to overwhelm homeostatic regulation?
Yes, temporarily
When are conditioned cues such as food advertisements more likely to stimulate overingestion?
Metabolic depletion - shortly before or during a meal because it amplifies their incentive salience, metabolic hunger makes us more responsive to cues signalling food and drug reward
What kind of signals does metabolic depletion send?
High levels of ghrelin, low levels of leptin, insulin, gut hormones and various metabolites that can act on the hypothalamus and brainstem and also brain areas involved in sensory processing, cognition, and reward.
Even in the absence of food advertisements, we are finding ourselves more and more …
Exposed to opportunities to eat - from a fixed meal pattern availability of food has increased everywhere - birthday cakes and vending machines at work and school, increasing number of fast food places, ready to eat food at refrigerator.
French paradox
Consumption of highly palatable French/Mediterranean cuisine produces less risk for obesity - factors other than palatability that lead to chronic overconsumption
What kinds of foods are addictive?
Energy dense foods that are high in sugar and fat and low in vitamins and minerals - empty energies
Dopamine signaling in the nucleus accumbens appears to play a role in?
Both the appetitive and consumatory phases of an ingestive bout
Is the decision to eat a food item up to the free will of every individual?
Conscious decisions may have a subconscious component - subconscious neural activity can guide ingestive behaviour before conscious explicit knowledge does
How does environmental signals affect food intake?
Interact with corticolimbic brain areas involved in cognition, emotion, motivation and decision making - bottom up by metabolic signals and can exert strong and overpowering top down control of food intake and energy balance regulation e.g. eating in complete absence of nutritional need.
