Appetite regulation Flashcards
what is the main centre for appetite regulation in the brain
arcuate nucleus
what is the arcuate nucleus next to
The arcuate nucleus is adjacent to the 3 rd ventricle.
what are the 2 main systems in the arcuate nucleus
There are 2 main systems in the ARC, one for inhibiting food and intake and the
other for increasing food intake.
what is an orexigen
- this is a substance that can increase food intake
- it activates specific neurological pathways to increase hunger and food intake
what can an orexigen be
- can be hormones or drugs
what can be an side effect of an oxreigen medication
increased weight gain
what is a desirable outcome of orexigen therapy
- cachexia Treatment
- AIDS/cancer
what neurones does the orexigenic pathway involve
It involves the NPY/AgRP neurones.
what is an anorexigen
- this is a substance that inhibits food intake
- activates specific pathways to reduce eating
what can an anorexigen be
- hormones or drugs
- there are currently no drugs to target this pathway
what neurones does anorexigen use
It involves the POMC/CART neurones.
How does nutrient sensation occur in the GI tract
- Food is broken down into nutrients in the GI tract - this happens by stomach acid, enzymes, gastric contractions and. mastication
- the nutrients pass into the duodenum and are broken down further
- these nutrients are then sensed by receptors in the GI tract
how do enteroendocrine cells sense the environment
- have receptors on their apical surface which sense the environment
- then they have vesicles which they release containing endocrine hormones
How Is the vagus nerve involved in appetite regulation
- has chemoreceptora nd mechanoreceptors
chemoreceptors
- these are activated by mediates released by the enteroendorcirne cells
- responds to nutrients, hormones, pH, osmolality
mechanoreceptors
- stimulated by stretch caused by …
- meal size
- gastric distentions hick causes satiety
is the vagus involved in long term or short term control of appetite
short term
how is the vagus linked to the arcuate nucleus
- arcuate nucleus connects with the dorsal vagus complex via the nucleus of tracts solitaires
what type of hormone is leptin
adipokine
where is leptin made
adipose tissue
is leptin anorexgien or an orexigen
anorexigne
is leptin long term or short term
Does not respond over short term but over longer term
what neurones does leptin activate and inhibit
Leptin is a satiety signal
- Inhibits NPY/AgRP neurones
- Activates POMC/CART neurones
what does a deficiency inception result in
A defect in leptin production or leptin receptors cause marked increases in AgRP
levels.
where is CCK synthesised
duodenum
what is CCK released in response to
fat and protein
what does CCK do
slows gastric emptying, releases bile and pancreatic enzymes
is CCK anorexigenic or orexigen
anorexigenic
what is PY released from and to
PYY is released from L cells in the GI tract
Released in response to high fat/protein
what does PYY do and what neurones does it activate and inhibit
Infusions lead to enhanced satiety
Directly inhibits NPY neurones and activates POMC neurones
Decrease food intake
is PYY short term or long term
Long term negative regulator of body weight
how does PYY work
Y1-5 receptors expressed peripheral/vagal/central
Y2 is specifically reported as primary receptor mediating effects
Is PYY anorexigenic or orexigenic
anorexigenic
what is insulin released due to
Insulin is released in response to increase plasma glucose levels
Released following meals
what does insulin inhibit and activate
Insulin is an acute satiety signal
- Insulin inhibits NPY/AgRP neurones
- Insulin activates αMSH/CART
is insulin anorexigenic or orexigenic
anorexigenic
what type of protein is glucagon like peptide -1
Most powerful known incretin in humans
what does GLP-1 do
Released in response to food intake
Decrease blood glucose
Decreases food intake
what is GLP-1 released by
L intestinal cell
what does GLP-1 activate and inhibit
GLP1 inhibits NPY neurones.
GLP1 also stimulates POMC neurones.
Is GLP-1 anorexigenic or orexigenic
anorexigenic
describe pancreatic polypeptide
Released in response to food intake, proportional to calories
Decreases appetite - anorexigenic
Long term energy balance
describe oxontymodulin
Anorectic peptide product of preproglucagon
Decreases ghrelin levels in plasma
May also increase energy expenditure
Effective weight loss
what is the only orexigen
Ghrelin
where is gherkin synthesised
Predominantly synthesised in the stomach
- it can also act via the vagus
what inhibits gherkin
Inhibited by food intake
Ghrelin is suppressed in proportion to the calories ingested
where are ghrelin receptors found
Ghrelin receptors found on NPY neurones.
Ghrelin stimulates NPY neurones to increase food intake directly.
Ghrelin follows a…
Follows a Circadian rhythm.
what are the short term and long term actions of gherlin
- short term contributes to hunger
chronic administration leads to hyperplagia (excessive eating)
malignant ghrelinoma causes persevered obesity
what are the problems with using Gherkin as a drug target
In obese subjects, ghrelin is low
Reducing ghrelin further may not assist with obesity
- Safety concerns on regulation of growth
- Also, prevent beneficial effect of ghrelin on cardiovascular system and inflammation
Ghrelin mimetics may be better suited to anorexia/cachexia
Infuse ghrelin increase food intake
name some other orexigenic peptides
- neuropeptide Y
- agouti related peptide
- melanin concentration hormone
- orexin
- galanin
there are different …
gut micrbiomes between obese and lean mice therefore there may be differences in humans
where is the hypothalamus located
below the thalamus
what are the 2 neuroendocrine functions of the hypothalamus
Direct neuronal connection to anterior pituitary
Hypophyseal portal system
what part of the hypothalamus controls food intake
Food intake is controlled by the lateral part of the ventromedial nucleus of the hypothalamus
- Known as the arcuate nucleus
what are the 2 groups of neuroendocrine neurones that are released from the hypothalamus
Neuropeptide Y (NPY) and Agouti related peptide (AgRP)- orexigens
Cocaine and Amphetamine related transcript (CART) and pro-opiomelanocortin (POMC)- anorexigens
- these have reciprocal inhibition
what is the primary role of the central orexigenic pathway
increase food intake
what neurones make up the central orexigenic pathway and what activates it and inhibits it
AGRP/NPY neurones in arcuate nucleus of hypothalamus
Activated by ghrelin
Inhibited by insulin and leptin
what does the central orexigenic pathway release
Releases NPY which activates Y1 receptors
Increase food intake by activating second order neurones
Inhibits POMC/CART neurones
what is AgRP
AgRP is a melanocortin receptor antagonist
- by blocking this receptor it increases food intake and decreased food inhibition intake
what neurones are released by the central anorexigeic pathway and what activates and inhibits it
POMC/CART neurones in arcuate nucleus of hypothalamus
Activated by insulin and leptin
what is the primary role of the central anorexigenic pathway
Decrease food intake by releasing melanocortins
how does the central anorexigenic pathway work
- it decreased food intake by releasing melanocortins
- main mealnocortin that it releases is α-melanocortin-stimulating hormone (α-MSH)
this works by ..
- activating second order neurones (MCR4 receptors)
- Inhibits NYY/AgRP neurones (MCR3 receptors)
what does deficiets in the anorexigenic pathway lead to
Defects lead to Hyperphagia and obesity.
Genetic deletion of MC4R in both humans and mice has been linked to severe,
hyperphagic obesity.
what causes an increase in fatty acid synthesis by malonyl CoA
Insulin and excess glucose increase fatty acid synthesis via Malonyl CoA.
what is malonyl CoA important in
Malonyl CoA is important in the synthesis of fatty acids.
Malonyl CoA also inhibits CPT1 to prevent Beta oxidation of FAs.
what is malonyl CoA controlled by
Malonyl CoA levels are controlled by AMPK.
Decreased energy (high AMP/ATP levels) increases AMPK levels.
When there is less energy more Malonyl CoA is activated so more FAs are made
what does serotonin do
An Anorexigenic molecule, decreases food intake.
- depletion of this promotes weight gain
how does serotonin decrease food intake
HTr2C increase POMC signalling (Anorexigenic).
HTr1B decreases AgRP signalling (Orexigenic).
what was a previous obesity treatment and why was it withdrawn
CB1 antagonist was used as an obesity treatment
- causes suicidal thoughts so it was withdrawn
what are the current obesity treatments recommended by NICE
Lifestyle/Behavioural modification
Fat absorption inhibition- orlistat
Bariatric surgery
what were the drug treatments used for obesity but withdrawn
Amphetamines- withdrawn
CB1 antagonists- withdrawn
GLP-1 agonists- type 2 diabetes but no clear effect on weight loss
5HT drugs- mixed with SSRIs, 5-HT2C effect modest, only in USA
