Endocrine control of food intake Flashcards
What decides whether you should be eating or not?
Hypothalalmus
What is the key part of the hypothalamus involved in regulation of food intake?
Arcuate nucleus
The arcuate nucleus is a circumventricular organ, what does this mean?
It has an incomplete blood-brain barrier so allows access to peripheral hormones
What are the two neuronal populations in relation to food intake?
Stimulatory- NPY and Agrp neurones
Inhibitory- POMC neurones
What do NPY and Agrp do to appetite?
Increase it
Under normal conditions, what is POMC broken down into?
alpha-MSH
What is alpha-MSH?
Endogenous agonist for MC4R which decreases food intake
In relation to MC4R, what is Agrp?
Endogenous antagonist
What happens when you need to eat?
You stimulate Agrp activity and block the inhibitory signal of alpha-MSH and stimulates food intake
Of the three proteins, which one is there a known mutation of associated with appetite?
POMC deficiency
What is POMC deficiency normally associated with?
Red hair and very pale skin
What does leptin do?
Tells the brain how much fat there is in storage so regulates eating
Where does leptin come from?
Fat
What happens in people that are leptin deficient ?
They think that they are starving all the time because there isn’t any leptin to tell the brain that there are fat stores
What would central or peripheral administration of leptin do?
Decrease food intake and increase thermogenesis- it activates POMC and inhibits NPY/Agrp
What are leptin levels like in fat people?
High- It circulates in plasma in concentrations proportional to fat mass
What happens with leptin in obese people?
They develop leptin resistance- ineffective as a weight control drug
What are the effects of no leptin?
Hyperphagia, lowered energy expenditure and sterility
What happens to children with no leptin?
They don’t go through puberty
Why don’t children with leptin deficiency go through puberty?
The hypothalamus won’t be releasing GnRH because leptin has a permissive effect on its release
Why do fat people have more insulin?
It circulates at levels proportional to body fat because fat people are more likely to be insulin resistant
What is the body’s largest endocrine gland?
GI tract
What is cholecystokinin involved in?
Gall bladder contraction
Gastrointestinal motility
Pancreatic exocrine secretion
What is secretin involved in?
Pancreatic exocrine secretion
What is GIP involved in?
Incretin activity
What is ghrelin involved in?
Hunger
Growth hormone release
What is gastrin involved in?
Acid secretion
What is pancreatic polypeptide involved in?
Gastric motility
Satiation
What is ghrelin released by?
Stomach
How many amino acids long is ghrelin?
28
What converts ghrelin to its active form?
Ghrelin O-acetyltransferase (GOAT)
How do ghrelin levels change throughout the day?
It is high in the morning then goes down after breakfast and rises again until lunch (the pattern repeats for every meal)
What effect does ghrelin have on appetite and how?
It increases appetite by directly modulating neurones in the arcuate nucleus:
Stimulates Agrp/NPY neurones
Inhibits POMC neurones
What is both PYY and GLP-1 secreted by?
L-cells
What shape are L cells?
Distinctive flask shape
What is PYY 3-36?
Fullness hormone that is released post-prandially
How does PYY 3-36 decrease appetite?
Directly modulates neurones in the arcuate nucleus:
Inhibits NPY release
Stimulates POMC neurones
What is the incretin effect?
If you give someone oral glucose you get a much bigger insulin response than when you give same amount of glucose IV
Why is there the incretin effect?
Glucose travelling in the GI tract stimulates the release of hormones that potentiate the effects of glucose-induced insulin release
What is GLP-1?
Gut hormone coded for by preproglucagon gene that is released post prandially and has an incretin role and reduces food intake
What are GLP-1 based drugs used to treat?
Diabetes mellitus
Why does GLP-1 not cause hypoglycaemia?
It only stimulates glucose-induced insulin release so it only works when it is needed and when there is low glucose, there is no insulin release
What is a problem with GLP-1?
It is quickly inactivated by DP-4 (dipeptidyl peptidase 4) so drugs have to be altered to have a longer half life
What is saxenda?
Long acting GLP-1 agonist- structure of GLP-1 has been tweaked so it’s more resistant to degradation, it also has a fatty acid group attached which stops it from being cleared from the circulation
It has recently been approved as a treatment for obesity and diabetes
What happens with high levels of PYY 3-36?
Nausea
What comorbidities is obesity associated with?
Depression Stroke Sleep apnoea Myocardial infarction Hypertension Diabetes Bowel cancer Osteoarthritis Peripheral vascular disease Gout
How much of body weight is due to heritability?
60-80%
What is the thrifty gene hypothesis?
Specific genes were selected for to increase metabolic efficiency and fat storage, evolutionarily sensible to put on weight, thin people don’t survive famine so don’t pass on their genes- evolutionary drive to put on weight
What is the adaptive drift hypothesis?
Used to be normal distribution of body weight:
Thin people will not survive/be able to reproduce
Fat people will be eaten
Eventually, improved at defending against predators so excess bodyweight became a neutral change
