Endo 14 - Endocrine control of food intake Flashcards
Bodyweight homeostasis can be influenced by?
- Ghrelin, PYY, other gut hormones
- Neural input from periphery and other brain regions
- Leptin
The paraventricular nucleus is a source of?
TRH
Where is the arcuate nucleus located
Either side of the 3rd ventral, above the median eminence
The arcuate nucleus is a key area in integrating peripheral and central feeding signals. How does it achieve this
Arcuate nucleus - has incomplete blood brain barrier - allows access to peripheral hormones
Arcuate nucleus has 2 neuronal populations - these neurones extend to other hypothalamic and extrahypothalamic regions:
- Stimulatory (appetite): NPY/Agrp neuron
- Inhibitory (appetite): (POMC neuron)
Explain the melanocortin system of food intake
MC4R on Paraventricular nucleus = decreases food intake
POMC neurones secrete a-MSH which stimulates MC4R - decreases food intake
Agrp neurones secrete agrp which inhibits MC4R - increases food intake
What are the rare human CNS mutations that affect appetite
POMC and MC4R deficiency found - they cause morbid obesity
No NPY/Agrp mutations discovered in humans
Describe leptin
How does leptin work?
Leptin - released from white adipose tissues- hence release is proportional to fat mass
Leptin receptors in hypothalamus (Ob-R)
Ob gene codes for leptin
It signals to the brain that there is enough fat - decreases food intake and increases thermogenesis
It activates POMC and inhibits NPY/Agrp neurones
Why is leptin ineffective as a weight control drug?
Most obese humans have high levels of leptin - so leptin resistance occurs.
Leptin present but doesn’t signal effectively
What can leptin absence cause
Hyperphagia (constant starving), lower energy expenditure, sterility
Giving leptin in these circumstances reduces obesity and may also restore LH/FSH pulsatility
What is the role of insulin in food intake
- Insulin = circulates at levels proportional to body fat
- Receptors in hypothalamus
- Central insulin administration reduces food intake
The GI releases more than …. different regulatory peptide hormones
20
GIT = largest endocrine organ
Ghrelin is known as the hunger hormone. How come?
It increases food intake by:
- Stimulates NPY/Agrp neurones
- Inhibits POMC neurones
Which type of cells secrete PYY and GLP-1?
L cells
secretory granules near basolateral membrane close to capillary
PYY is the satiety hormone. Why
It is released after meals - reduces appetite by:
- Inhibits NPY release
- Stimulates POMC neurons
- Decreases appetite
What gene codes for glucagon like peptide 1 (GLP-1) and when is GLP1 released
Coded for by Preproglucagon gene
GLP-1 is a gut hormone released after eating (post prandially)
GLP-1 is an incretin. What is an incretin
Incretins = hormones that:
- Released after eating
- Stimulate insulin secretion from B-islet cells in pancreas
GLP-1 is mimicked to treat T2DM (GLP-1 agonists / DPP-4 inhibitors) - DPP4 breaks down GLP-1
What is the GLP-1 analogue used that is long acting
Saxenda (liraglutide)
Double the dose used for T2DM
Thrifty gene hypothesis - explain
Basically, in cavemen times it was better to have fat storage as famines and stuff happened. But now we don’t need to run around to catch food etc so it predisposes to obesity. Thin humans didn’t survive famines so couldnt pass genes
Adaptive Drift gene hypothesis - explain
Normal distribution of weight - because fat people were eaten and thin people didn’t survive
Humans also learned to defend themselves against predators - so obesity wasn’t selected against
as fat people could defend themselves
Putting on body fat then became a neutral change - dint affect chances of survival so much
Leptin and insulin signal long term food intake. What signals to regulate short term food intake
GIT
