Endo 13 - Endocrine Control of Food Intake Flashcards
What is the name of the part of the hypothalamus which is involved in the regulation of food intake?
Arcuate nucleus
What is a specialised feature of the arcuate nucleus which allows it to integrate central and peripheral inputs?
Circumventricular organ
- incomplete blood brain barrier so exposed to peripheral hormones
What are the two neuronal populations in the arcuate nucleus?
- Agrp/NYP - Stimulatory
2. POMC - inhibitory
Describe how the melanocortin system works
Under normal conditions, POMC is broken down into alpha MSH
alpha MSH is a agonist of MC4R and prevents food intake
When you need to eat, Agrp activity will increase, blocking MC4R receptor, therefore increasing food intake
Name two types of mutations which affect the melanocortin system
- POMC deficiency - associated with pale skin, red hair and obesity
- MC4R mutation - associated with obesity
What are the features of the ob/ob mouse?
- obese
- diabetes
- infertile
- decreased energy expenditure
- decreased body temperature
- stunted growth
What is leptin?
Released from fat and tells the brain how much fat there is in storage so regulated eating
What is the effect of leptin administered centrally on leptin deficient individuals?
Decreases foot intake
increases thermogenesis
What effect does leptin have on the melanocortin system?
activates POMC and inhibits Agrp neurones so activates MC4R and decreases food intake
Why does leptin treatment not work as an anti-obesity drug?
Leptin circulates at levels proportional to fat mass
So obese people have high leptin
high leptin = more resistance
Why won’t people with leptin deficiency go through puberty?
Without leptin, GnRH release is stopped
so less LH and FSH so puberty cannot happen
Insulin circulates at levels…
that are proportional to body fat
Describe the central effects of insulin
reduces food intake
chronic - reduced body fat
acute - reduced intake of sugar
What is ghrelin?
Hunger hormone
What organ releases ghrelin?
Stomach
What is ghrelin activated by?
Ghrelin O Acyltransferase - GOAT
What effect does ghrelin have on the melanocortin system?
stimulates NPY/Agrp neuones
inhibits POMC
so inhibits MC4R
so increases food intake
Which cells of the GI tract release PYY and GLP-1?
L- Cells in the distal small intestine
When is PYY released?
Post meal - depends on size of meal
What are the effects of PYY?
stimulates POMC neurones so decreases food intake
What is the effect of GLP-1?
decreases food intake
What is the incretin effect?
Giving someone oral glucose will achieve a higher spike insulin that if you give the same amount of glucose IV
What makes the incretin effect work?
glucose travelling in the GI tract potentiates the effect of hormones
Describe the degradation of GLP-1?
Broken down very quickly - half life of less than 1 min
Name a long acting GLP-1 receptor agonist that is used for diabetes and obesity?
Saxenda
What is the problem with PYY as a drug target?
Narrow therapeutic window
causes nausea
What are the comorbities associated with obesity?
stoke, mi, cancer, diabetes, hypertension
What is the thrifty gene hypothesis?
evolutionarily sensible to put on weight to survive scarcity
What is the adaptive drift hypothesis?
used to be normal distribution of weight
predators would kill fat people
but we got better at evading predators
so more likely to put on weight now
