Vagal afferent control of food intake - neuromodulation of food intake Flashcards
How does adiposity work ?
it works as a negative feedback loop
circulating signals inform brain of available energy stores the brain can alter our food intake
also important for regulating energy expenditure
What peripheral signals regulate long term energy balance and where do they come from ?
they help the brain integrate information
leptin is released from adipose tissue and insulin is released from the pancreas
What form does nutritional info take to provide feedback to the brain ?
absorbed nutrients, neuronal signals and gut peptides
What info does the vagus nerve relate to the brain from the stomach and upper small bowel and where does it send it to ?
stomach distention and the chemical and hormonal milieu of the upper small bowel to the NTS
What actions do hormones released from the gut have ?
incretin, hunger and satiety stimulating action
incretin hormones, GLP-1, GIP and potentially OXM improve the response of endocrine pancreas to absorbed nutrients
Where is OXM and PYY released from ?
released from lower GIT
Where is PP released from ?
released from islets of langerhans
What does GLP-1 and OXM do ?
they reduce food intake
What does gherlin and cck do ?
ghrelin is released from stomach and it stimulates appetite
whereas CCK is a gut hormone which stimulate satiety as it feeds back to the vagus nerve
What hormones can travel up the vagus nerve to alter food intake and what effects do they have ?
leptin and CCK are involved in inhibiting food intake
grehlin and orexin are involved in promoting food intake
these signals travel up to the NTS and hypothalamus
the majority are involved in inhibiting food intake
if they come from the intestine then they inhibit food intake (CCK, GLP-1 and PYY)
if they come from the stomach then they can do both so it depends on state of stomach, full or empty
What was one of the first things to be discovered to treat obesity ?
CCK because it initially reduces meal sizes
in rats they infused them with CCK and measured their food intake and meal size
- it rapidly reduced their food intake
Why did the CCK infusion not work ?
although meal size reduced, their meal number increases so initially there was a decrease in food intake but then it crept up again
the effects were lost after a few days
the food intake increases and rebounds as if there is a set point of normal weight
What effect did CCK infusion have on body weight ?
it stayed pretty much the same
What experiment was carried out to prove that CCK worked via the vagal nerve ?
took rats and intraperitonally injected them with capsaicin
at high doses it kills cells via the vaniloid receptor which is predominantly present on sensory neurones so it killed some nodose cell ganglions cells which is where the vagal afferent cell bodies are
then they looked at the effect of CCK infusion
What effect did CCK have when the rats were pretreated with capsaicin?
had less effect on reduction in food intake compared to control rats with sensory neurones intact
therefore killing sensory cells in this way seems to affect food intake
this effect was also reduced when the 4th ventricle was pretreated with capsaicin- kills sensory neurones via endings in NTS
What experiment was carried out to compare vagal afferents and efferents in food intake ?
they cut the vagus as it went to the stomach, just below the diaphragm
also cut just the afferents as they go into the brainstem
tried cutting efferent- vagal roots as they left the brainstem
What results were shown when they carried out the lesions to the vagal afferents and efferents?
CCK didn’t have much of an effect when afferents were cut so therefore the reduction in food intake was prevented
whereas when the efferents were cut there was an increased % inhibition demonstrating that the efferents are not important for helping CCK reduce food intake
What experiment was carried out to test leptin ?
produced leptin receptor ko sensory neurone mice using cre recombinase
did they expressing cre recombinase in neurones with a specific sodium channel
used immunofluorescence to prove KO in nodose ganglion
What happened when leptin receptor was KO of sensory neurones in nodose ganglion ?
didn’t affect light phase(day), but increase meal duration in dark phase (night)
- mice are nocturnal so they dont normally eat much during the day
- due to increased meal size they had increased body weight compared to controls- got fatter
- increased fat mass in subcutaneous, epididymal, mesenteric and retroperitoneal
What mistake is often made when carrying out food intake experiments on rats/mice?
do a lot of experiments during the day but this is when they should be asleep so it could affect results
What happens when grehlin concentration is increased and where does it act?
it stimulates food intake which increases as doses increase
when the vagus nerve is cut the effects of grehlin are altered so it must act via the vagus nerve
- destroyed sensory nerves with capsaicin and the effects of gherlin were reduced
How did they show that grehlin was involved in increasing food intake ?
they infused rats with gherlin, some of the rats were pretreated with capsaicin so the effects of gherlin were abolished
- there was no c-fos labelling in the capsaicin treated rats but there was c-fos labelling in 3rd ventricle, hypothalamus demonstrating increased activity - in control rats there was c-fos activity in neurones of arcuate nucleus, of NPY neurones and GHRH neurones in ARC
Where is the gherlin receptor present and how was this determined?
using PCR, took nodose ganglions and mashed it up to look for mRNA
also used in situ hybridisation
in the nodose ganglion and hypothalamus the gherlin receptor is present
receptor is produced in vagal nerve cell and transported to terminal
What often co-localised with ghrelin receptor?
the vanilloid receptor
