Appetite Regulation Flashcards
What is an orexigen?
A substance that increases food intake (appetite sitmulant)
- can be hormones or drugs
- unwanted side effect of medication (increase weight gain)
- desirable outcome of medical therapy
- activates specific neurological pathways to increase hunger/food intake
What is anorexigen?
Substance which inhibits food intake (appetite inhibiting)
- hormones or drugs
- activates specifical neuronal pathway altering eating behaviour
- no current drugs target this pathway
How is food broken down in the GI tract?
Mastication Stomach Acid Proteases Rhythmic gastric contractions
Where do ingested nutrients pass?
Into the duodenum where there are bile acids and pancreatic enzymes
- sensed by receptors in the GI tract
What are the properties of enteroendocrine cells?
- specialised cell found in the duodenum downwards
- sense the luminal environment
- pyramidal shape allowing them to be projected out into the lumen detecting environment when nutrients enter the gut
- Top luminal part ‘tastes’ the nutrient environment
- Basal part contains vessels for endocrine hormone release
How do enteroendocrine cells release signalling molecules/hormones?
- nutrients activate to their complementary specific GPCR on apical side of enteroendocrine cells activating them
- this results in vesicular release of hormones on the basal side of the enteroendocrine cells
- Hormones bind to vagal afferents (neuronal endings next to endocrine cells) of the extrinsic nervous system of the gut
- excitation of the nerve causes hormone release
What do vagal afferents outside of the enteroendocrine cells respond to?
Nutrients, pH and osmolality
What types of receptors are on vagal afferents?
- chemoreceptors detecting released hormones
- mechanoreceptors stimulated by stretch (gastric distension and meal size)
What is the nervous system of the gut?
- intrinsic neural system (enteric)
- extrinsic neural system (gut connecting with the CNS mediated by the vagus)
- pelvis and splanchnic nerves in the distal GI
What is the vagus connected to?
The arcuate nucleus in the hypothalamus
What does the arcuate nucleus contain?
connects NTS, dorsal motor nucleus of the vagus nerve, area prostrema
What is leptin?
Circulating satiety factor
Adipokine - made by adipose tissue
LT response
Secretion related to time
What is the function of leptin
- Anorexigenic - inhibits food intake/appetite inhibiting
- Inhibits NPY/AgRP neurones and activates POMC/CART neurones
- Increases bp, regulates thyroid hormone synthesis, reduces insulin secretion, increases heart rate, regulates bone mass, regulates menstrual cycle, regulates appetite/metabolism/energy, activates immune cells
- increases when there is increased body fat = obese individuals are leptin resistant
What is CKK?
Cholecystokinin
Synthesised in the duodenum
What is the function of CKK?
Released in response to fat and protein
Slows gastric emptying, releases bile and pancreatic enzymes
Activates vagus leading to satiety
If levels are too high it creates nausea and taste aversion
What is PYY?
Peptide YY
Released by L cells in the GI tract
Released in response to high fat and protein
What is the function of PYY?
Inhibits NPY neurones and activates POMC neurones
Leads to satiety
Reduced food intake
LT body weight regulator
Acts on Y receptors in peripheral, vagal and central mechanisms
If too high creates nausea
What is the function of insulin on appetite?
Acute satiety signal
Inhibits NPY/AgRP neurones and activates CART/aMSH
What is the function of GLP-1?
Glucagon like peptide -1 most powerful incretin Released in response to food intake Lowers blood glucose and food intake Reduced in obese subjects
What is the function of oxontymodulin?
Decreases plasma ghrelin levels and energy expenditure
Is an anorectic peptide product of peproglucagon
Effective weight loss
What is the function of PP?
Pancreatic polypeptide
Released on food intake
Decreases appetite
LT energy balance
Which peptides are arexorgenic?
Leptin CKK PYY Insulin GLP-1 PP Oxontymodulin alpha-MSH CART Corticotropin-releasing hormone
Which peptides are orexigenic?
Ghrelin NPY AgRP Orexins Galanin Melanin-conc. hormone
What is ghrelin
Major orexigenic hormone (hunger hormone)
made in the stomach
Circulating so acts directly in hypothalamus via vagus and on brainstem receptors
Infuse ghrelin used for anorexia/cachexia to increase food intake
Inhibited by food intake
Suppressed in proportion to calorie ingestion
What is the function of ghrelin?
ST = meal initiator = hunger
LT if chronically administered = hyperphagia, malignant ghrelinoma, preserved obesity
Effects: glucose homeostasis, gut motility, pancreas function, inflammation
What are the 2 neuroendocrine functions of the hypothalamus?
- direct neuronal connection to anterior pituitary
- hypophyseal portal system
What role does the hypothalamus have in metabolism?
Regulates metabolic rate as influences pituitary function, feeding, stress response, water balance, sleep-wake cycle and thermoregulation
What are the neuroendocrine neurones in the hypothalamus?
- orexigens -> NPY and agouti-related peptide
- anorexigens -> CART and POMC
reciprocally inhibit each other
signals from the plasma control their activity
What is the central orexigenic pathway?
NPY and AgRP neurones are in the arcuate nucleus
Get activated by ghrelin
Release NPY which activates Y1 receptors
Activates 2nd order neurones increasing food intake and inhibiting POMC/CART neurones
What is AgRP an example of?
Melanocortin receptor antagonist
What is the central anorexigenic pathway?
POMC/CART activated by insulin and leptin
Releases melanocortins
This decreases food intake
What is the main melanocortin?
alpha-melanocyte stimulating hormone
activates 2nd order neurones (MCR4 receptors)
inhibits NYY/AgRP neurones (MCR3 receptors)
What is the role of malonyl-CoA?
- Appetite controller
- Inhibits lipolysis (carnitine shuttle) at high levels
- When we are not hungry malonyl-CoA levels increased in cytoplasm for FA synthesis
& hypothalamus senses high levels and so turns down AgRP and NPY to decrease appetite - When hungry less malonyl-CoA in cytoplasm so no FA synthesis, sensed by hypothalamus and AgRP and NPY increased
What is the role of cannabinoids?
Increase appetite and consumption of food = high expression of CB1 receptor in the hypothalamus
