Endocrine Control of Food Intake Flashcards
(28 cards)
Which key area of the hypothalamus is involved in the regulation of food intake?
Arcuate nucleus
What feature of this area allows it to integrate central and peripheral inputs?
It’s a circumventricular organ (has an incomplete BBB)
Allows access to peripheral hormones
What are the 2 neuronal populations in the arcuate nucleus?
Agrp/NPY = stimulatory (increases appetite) POMC = inhibitory (decreases appetite)
Describe how the melanocortin system works.
Under normal conditions, POMC is broken down to alpha-MSH, which stimulates the MC4R receptor + prevents food intake
When you need to eat, there will be an increase in Agrp activity
Agrp will block the MC4R receptor + stimulate an increase in food intake
State 2 CNS mutations that affect this system and can cause obesity.
POMC deficiency: associated with obesity, red hair + pale skin
MC4R mutation: associated with obesity
NO known Agrp or NPY mutations
What are 7 features of the leptin deficiency ob/ob mouse?
Obesity Diabetes Decreased energy expenditure Decreased body temperature Infertility Stunted linear growth Decreased immune function
What is leptin?
167 AA hormone
Produced by adipocytes + signals to the brain, telling it how much fat there is in storage
High when high body fat
What effect does centrally administered leptin have on leptin deficient individuals?
Decreases food intake
Increases thermogenesis
What effect does leptin have on the melanocortin system?
Inhibits Agrp/NPY neurones (which increase appetite) Stimulates POMC (which inhibits appetite) Result = decrease in energy expenditure
What issue do obese people without leptin deficiency have, which means that leptin treatment is not effective as an anti-obesity drug?
Circulating leptin is usually proportional to body fat mass
Most fat humans have high leptin
So a lot of obese people are leptin resistant (doesn’t signal effectively)
Why won’t people with leptin deficiency go through puberty?
Leptin has a permissive effect on GnRH release
Without GnRH release, you will not get sufficient LH + FSH release to cause puberty
Also cause of severely underweight getting secondary amenorrhoea
Describe the central effects of insulin.
Insulin has a similar effect to leptin as it reduces food intake
There are insulin receptors in the hypothalamus + insulin circulates at levels proportional to body fat
Thus fat people have higher insulin resistance + pancreas must produce more to have an effect
What is ghrelin and how is it activated?
Hunger hormone released by the stomach (28 AA’s long)
Activated by Ghrelin-O-acyltransferase (GOAT), which adds a fatty acid to the 3rd AA in the chain
What effect does ghrelin have on the melanocortin system?
Stimulates Agrp/NPY neurones
Inhibits POMC neurones
Increases appetite
Which cells of the GI tract release PYY and GLP-1?
L-cells
What are the effects of PYY3-36? When is it released?
Stimulates POMC neurones
Inhibits NPY neurones
Decreases appetite
Released post-prandially
What is GLP-1, what gene encodes it and when is it released?
Glucagon-Like Peptide 1
Encoded by pre-proglucagon gene
Released post-prandially
What are the effects of GLP-1?
Important role in the incretin effect: stimulating glucose-stimulated insulin release
Decreases food intake
Describe the degradation of GLP-1.
Rapidly broken down by dipeptidyl peptidase-4 (DP-IV)
Half-life: ~1 minute
State a long-acting GLP-1 receptor agonist that is used for diabetes and obesity.
Saxenda
What is the problem with PYY 3-36 as a drug target?
High levels of PYY can cause nausea
Only a relatively small sweetspot, in terms of concentration, that will have beneficial effects
State 8 comorbidities associated with obesity.
Stroke Depression Sleep apnoea MI Cancer Diabetes Hypertension Osteoarthritis
What is the thrifty gene hypothesis?
It was evolutionarily sensible to put on extra weight because it meant that we could survive the times when food was scarce (thinner people would die in these times)
What is the adaptive drift hypothesis?
Used to be a normal distribution in terms of body weight
Predators would kill fat people
We improved at evading predators so increased body weight because a neutral change
