endocrine control of food intake Flashcards
draw a diagram to illustrate how the hypothalamus regulates appetite *
–
what are the 2 factors in body weigt homeostasis
food intake and energy expenditure
what are the factors that influence the body weight homeostasis that act on the hypothalamus *
ghrelin, PYY and other gut hormones
neural input from the periphery and other brain regions
leptin
how is the hypothalamus involved in food regulation *
integrates lots of inputs
eg vagal nerve from GI to brainstem tell hypothalamus how much stomac has stretched
hypothalamus determines whether you should feel hungry
what is te arcuate nucleus, where is it and what does it do *
key brain area involved in regulation of food intake
at base of brain below the circle of willis
as incomplete blood brain barrier ie is a circumventricular organ - so has access to peripheral hormones - as idea of the peripheral feeding state
it integrates peripheral and central feeding signals
what are the neuronal populations in the arcuate nucleus and what do they do *
NPY/Agrp neurons are stimulatory- increase appetite
POMC neurons - decrease appetite - POMC is chopped into alpha MSH wich suppresses food intake
both neurons extend to other hypothalamic and extra-hypothalamic regions - circuits to higher centres
explain how mutations in neuronal pathways controlling food intake affect weight balance *
no NPY/Agrp mutations - in mice when induce in development - brain adjusts accordingly
POMC deficiency and MC4-R mutations = morbid obesity, also pale skin and red hair because of lack of other POMC products also POMC codes for ACTH so stress axis doesnt work. if have melanocortin receptor deficiency - just have problems with food regulationn
are mutations in neuronal pathways responsible for obesity epidemic *
no - obesity is polygenic
if you have monogenic mutation causing obesity - you are obese from a very young age
what kind of mutation is the ob/ob mutation *
recessive
characteristics of the ob/ob mouse *
obese
diabetic
infertile
stunted linear growth
decreased body temp
decreased energy expenditure
decreased immune func - immune system energetically expensive - sut down if you are staving
similar abnormalities to starved animals - thinks starving to death so eats loads
what is leptin *
protein hormone
made form fat tissue to tell the brain you’re not starving
it is what is missing in the ob/ob mouse
describe leptin’s role in food intake *
low levels when body fat is low
igh wen body fat is high
central/peripheral admin = reduced food intake and increased thermogenesis
activats POMC and inhibits NPY and Agrp neurons
why is leptin ineffective as a weight control drug *
fat people develop leptin resistance - it is present at igh levels just doesnt signal effectively
wy is leptin considered a ‘hormone of absence’ *
when it is missing, there are profound effects
hyperphagia, lowered enrgy expenditure and sterility (switces off the reproductive axis)
antistarvation hormone rather than an anti-obesity one
what is the effect if your body as never seen leptin *
dont go through puberty - reproductive axis has been switched off
obese
when give recombinant leptin = reactivation of the system = lose weight and begin puberty - not resistant, yiu’re just missing leptin
leptin also restores LH pulsitility in people with ypothalamic amenorrhoea
why is puberty earlier in teh developed world
people are better nourised so have higher leptin
what time frame signal is leptin and insulin with regard to reducing food intake
long term
describe insulin’s role in food intake 8
circulates at levels proportional to fat - tis is the basal insulin - more weight means pancreas works harder to produce basal insulin = insulin resistance
receptors for insulin are in the hypothalamus
central administration reduces food intake
describe gut hormones *
there are >20 regulatory peptide hormones
influence gut motility, secretion of other hormones abd appetite
their release depends on the nutrient level in the gut
where is ghrelin released from *
the stomach
describe how and when gut hormones are released *
enterendocrine cells can detect fats - see if they are short chain or long chain, carbs - transporter mech tat takes glucose into cell changes electrical state and uses downstream signalling, and protein products
then releases combinatioon of gut hormones from the basal side of the cell
hhormones have an endocrinbe effect acting on panc or brain, paracrine effect altering secretions or effect neuronal function of enteric nervous system or vagus
what is ghrelin *
28aa gut hormone
has fatty acid chain - necessary for receptor binding and movement in the circulation
ghrelin o-acyltransferase - attach FA chain
what is the role of ghrelin *
it increases appetite and drives when you want to eat by acting on the arcuate nucleus
it stimulates nPY/Agrp neurons
inhibits POMC neurons
increases food intake
what is satiation *
stop eating present meal
what is satiety *
how long you fell full - controls pattern of food intake
what do L cells release *
PYY and GLP-1
describe how the structure of an L cell relates to function *
it is flask shaped - open cell
has end near lumen with all the sensory machinary
signal modulates teh release of the secretory granules from the broad base on a capillary
also have neuro/pseudopods that communicate directly with the neurons by releasing tracers that synapse with the neurons so propagate a neuronal signal that way
what is PYY and whatbdoes ot do *
it is a 36 chain aa
directly modulates neurons in the arcuate nucleus
inhibits NPY
stimulates POMC neurons
decreases appetite
eat less - brain thinks tat you have just eaten
wat is GLP-1 *
gut hormone coded for by the preproplucagon gene and released post-prandially
pre-proglucagon gene is in L cells
chopped into GLP-1 used to treat diabetes and obesity
GLP-2 involved in gut growth perhaps treatment for intestinal disease
the end og GLP-1 is quickly cleaved so GLP-1 is turned off - has a short half life
it has the incretin role - stimulate glucose stimulated insulin release
incretins are hormones tat detect glucose form the gut, released from the gut and detected by the pancreas
reduces food intake
how can we use GLP-1 therapeutically *
modulate it
GLP1 agonists that bind to GLP1 receptor but ave a longer half life
and DPP4 inhibitors - suppress the breakdown of endogenous GLP1
what is saxenda *
it is a long acting GLP-1 receptor agonist
ave fatty acid attached to help it move through the circulation
have arg aa so that it is not broken down
use double the dose you would use for t2dm and it can cause weight loss to help with cardiovasscualr disease
other than glp1 and 2 what does pre-proglucagin get converted into and where
glucagon in a cells of the pancreas
what are the 3 types of satiety action caused by gut hormones 8
post-prandial - reduces food intake following a meal - pyy and glp-1
chronic - gut disease, chronic elevation suppresses appetite - reduce stress in gut and give it a chance to recover
acute nausea - toxic ingestion, acutely very high levels - toxins bind to receptors and cause surge in hormones - signal that you shouldnt be eating it so it makes you sick
what is the possibility of using gut hormones as drugs *
use a combination to reduce food intake by suppressing appetite
what is the difficulty of using gut hormones as drugs 8
have to inject a high amount for it to have an effect
if inject too much = nausea
level rapidly decrease because have short half life
only in the anorexigenic range for a short period of time
have to alter the pharmacokinetics of the drugs so they last longer
what is the possibility of dietry manipulation to alter food intake 8
understand how the gut detects food and hijack these systems
eg use synthetic nutrients to stimulate nutrient receptors - spark enteroendocrine cells to fire - feel like get calories but dont have to eat as much
or get food to target the lower gut, because the bigger the meal the lower the food goes down to the gut, therefore have longer satiety - if you can get smaller meals to lower end of gut you drive satiety without eating too much
what are the comorbiditiees assoiciated with obesity *
depression
sleep apnoea
bowel cancer
osteoarthritis
gout
stroke
mi
hypertension
dm
peripheral vascular disease
how do genetics influence weight gain *
in given env genetics determine how much weight you put on
monozygotic twins have a higher concordance than dizygotic twins
ie if one monozygotic twin is obese the other has a higher chance of being obese than if they were dizygotic twins
what is teh thrifty gene hypothesis 8
specific genes are selected for to increase metabolic efficiency and fat storage when cavemen - thin humans didnt survive famines so didnt pass their genes on
in context of plentiful food these genes predispose obesity
populations previously prone to starvation become most obese when exposed to western diet
what is the drifty gene hypothesis *
in the past there was a normal distribution of body weight - the fat are eaten and the thin starve
but now obesity is not selected against
genetic druft is putting on body weight and there being a neutral change ie inheriting genes that mean you put on weight
however in current context the people who inherit these genes put on weight
in a toxic environment those who are genetically prone will put on more weight
what time frame do gut peotides prevent food intake over
short term
effect of leptin on hypothalamo-gonadal axis *
leptin is permissive of it - ie hig leptin means axis works
wat does POMC split into that is involved in food regulation *
aMSH
where are POMC neuronal cell bodies *
te arcuate nucleus
name for arcuate nucleus in humans *
infundibular nucelus
what is teh role of a melanocyte stimualting hormone *
endogenous agonist of melanocortin 4 receptor
what neurons does ghrelin stimulate
orexigenic agrp
where is glp-1 produced
from the pre-proglucagon gene in l cells in the gut
