Endo 15: Endocrine control of food intake Flashcards
What is the input to the hypothalamus
GHRELIN, PYY & other gut hormones
Neural input from the periphery and other brain regions
LEPTIN
What are the outputs of hypothalamus
Food Intake
and
Energy Expenditure (TRH)
Why is paraventricular nucleus important
Releases TRH
Where is arcuate
Bottom of hypothalamus next to the 3V
How does arcuate receive hormonal input. What function does arcuate nucleus serve
Incomplete blood brain barrier, allows access to peripheral hormones.
(circumventricular)
Integrates peripheral and central feeding signals.
What are the key neuronal populations in the arcuate nucleus
Stimulatory (NPY/Agrp neuron)
Inhibitory (POMC neuron)
How is POMC used in different brain areas
pituitary cut up to ACTH
Hypothalamus cut up to MSH
What hormone is present in the paraventricular nucleus and the function
MC4R…. reduces appetite
How does POMC neuronal bodies affect paraventricular nucleus
Releases a-MSH to stimulate PVN to decrease food intake
How to AGRP/NPY affect PVN
releases AGRP which inhibits MCR4 so increased appetite
T/F NPY and Agrp mutatuons are responsible for obesity prevalence
F!! POMC deficiency and MC4-R mutations cause morbid obesity, but NOT responsle for obesity prevalence
What does the hypothalamus receive signal from
From leptin, the gut and brainstem as well as cortical regions
What is the ob gene, what occurs in deficiency
Ob gene codes for leptin in ob/ob mouse there is no leptin, nothing to tell the brain that there are adequate fat stores in the adipose tissue
Profoundly obese. Hyperphagia. Diabetic. Decreased body temperature. Decreased energy expenditure.
What is leptin, where is it released, and where are its receptors
Leptin released from WHITE adipose tissue
Leptin receptors in the hypothalamus (Ob-R)
How does leptin work on the hypothalamus
Activates POMC and inhibits NPY/AgRP neurons.
What is the effect of central or peripheral administration of leptin in those who have deficiency
Central or peripheral administration decreases food intake and increases thermogenesis.
What will leptin be when body fat is
a) high
b) low
a) high when body fat high
b) low when body fat low
With obese humans, what are leptin levels like
Most obese humans have high leptin (high fat mass)….
Can leptin be used as a weight control drug
No, leptin is ineffective as a weight control drug.
the brain is now unresponsive to leptin because it’s been high due to high adiposity
What is the role of inslin in food intake.
T/F insulin secretion from the pancreas increases in proportion to body adiposity
Insulin circulates at levels proportional to body fat.
Receptors in the hypothalamus.
Central administration reduces food intake.
T! Glucose-induced insulin secretion from the pancreas increases in proportion to body adiposity, owing to the capability of expanding fat stores to induce resistance to insulin’s glucose-lowering effects.
What is the body’s largest endocrine organ
The gut
How many gut hormones are there
20+
What do gut hormones control
gut motility, secretion of other hormones, appetite.
Rlease of gut hormone is regulaated by what
Release regulated by gut nutrient content.
How dows grehlin impact appetite. Where is grehln released
Released in stomach
It stimulates NPY/Agrp
Imhibits POMC
INCREASES appetite
What type of hormone makes you feel full?
PYY (satiety)
How does PYY work and where is it released
Released from L cells in intestine
Inhibits NPY release.
Stimulates POMC neurons.
Decreases appetite.
What is GLP1 and what is the effect on appetite
T/f: GLP1 is made from the same gene as glucagon. PYY also comes from this gene.
Gut hormone coded for by the preproglucagon gene and released post-prandially in the L cells by the gut
F: glucagon, glp1 and glp2 from same gene but PYY from elsewhere
What type of hormone is GLP1….. explain this hormone type
Hormones that
Are released after eating
Augment insulin secretion from b islet cells
2 functions of GLP-1
Well characterised incretin role and also reduces food intake.
Are there therapeutic uses of GLP1
GLP-1 agonists are injectable only
or
DPP-4 inhibitors (DPP-4 endogenousl breaks down GLP-1, so these drugs prevent breakdown)
Why is it difficult to give injection for GLP-1
How is GLP-1 agonists used in type II diabtetes
Very short lives as they’re peptide hormones so are broken down,,,, haf life just 1 minute, so can be modified to saxenda (which is modified GLP so longer lived)
Used in type II diab. because they can cause increased release of insulin to control sugar and also inhiit appetpite
Also have recently been licensed for obesity treatment
Coud PYY3-36 be used a as a drug target
No because narrow therapeutic window and cause nausea above this, and no efffect below it
What is thrify vs drift gene
thrifty gene stated that those who had genes that caused storage of fat were selected for as starvation was a big problem in cave men times. This shows as Populations historically prone to starvation become most obese when exposed to Western diet and sedentary life-style (e.g. Pima Indians, Pacific Islanders).
drfity gene says that there is normal distribution of body mass, as if you are too fat you are eaten and if you are too thin then you starve.
BUT then 20,000 years ago people learnt to defend against predators so obesity isn’t selected against…. so body fat was then a neutral change/genetic drift….
In a healthy environment those genetically prone will have same BMI as everyone else but in toxic environment i.e. like the western fat diet one, then these people will put on lots of weight
Which gene codes for leptin
The Ob gene
