Obesity and the endocrine control of food intake Flashcards
How is your body weight homeostasis regulated?
Input:
- Ghrelin, PYY and other gut hormones
- Neural input from the periphery
- Leptin
Process: Hypothalamus
Output:
- Food intake or Energy expenditure. Decide whether you should be eating or not
Draw the anatomy of the hypothalamus
See diagram
What is the arcuate nucleus?
Arcuate nucleus - involved in the regulation of food intake. It is a circumventricular organ meaning it has access to peripheral hormones. This allows the arcuate nucleus to integrate peripheral and central feeding inputs.
What are the neuronal populations in the arcuate nucleus?
Stimulatory (increase appetite) - NPY + Agrp neurons
Inhibitory (decrease appetite) - POMC neurons
Both sets of neurones extend to other hypothalamic and extra-hypothalamic regions
Describe the melanocortin system
MC4R (in the paraventricular nucleus) - decreases food intake
1) alpha-MSH: agonist of MC4R
2) Agrp: antagonist of MC4R
POMC is broken down to alpha-MSH. Both a-MSH and Agrp are released from the arcuate nucleus
E.g if you want to eat, you increase Agrp activity, block the inhibitory signal of a-MSH and stimualtes food intake.
Describe some CNS mutations affecting appetite
- No NPY or Agrp mutations associated with appetite discovered in humans.
- POMC deficiency and MC4-R mutations cause morbid obesity.
What is leptin?
- 167 amino acid hormone
- Released from fat and tells the brain how much fat there is in storage thus regulating eating
- People who are leptin deficient will think they are starving all the time because there isn’t any leptin to tell the brain there are fat stores
- Central or peripheral administration of leptin will decrease food intake and increase thermogenesis
What does leptin activate?
Activates POMC and inhibits NPY/Agrp neurones
Describe leptin resistance
Leptin circulates in plasma in concentrations proportional to fat mass
- Fat humans have high leptin; they are however leptin resistant. (leptin doesn’t signal effectively)
- For patients like this leptin is an ineffective weight control drug.
What are the effects of the absence of leptin?
- Hyperphagia
- Lowered energy expenditure
- Sterility
- The absence of leptin has a permissive effect on GnRH release from the hypothalamus. Leptin is required for puberty. It is an effective treatment for patients with leptin deficiency.
What is a cause of amenorrhoea?
Low body weight = low leptin. There is no pulsitile release of LH and FSH.
Describe the role of insulin in food intake
- Circulates at levels proportional to body fat; this maybe due to the fact fat people are more likely to be insulin resistant = more insulin required
- There are insulin receptors in the hypothalamus
- Reduces food intake like leptin
What effects may insulin in the brain across the BBB?
Chronically - reduce body fat
Acutely - If you have a big glucose load you should suppress having more sugar
What is Ghrelin?
“hunger” hormone
Released by the stomach
It is 28 amino acids long
There is a fatty acid on the 3rd amino acid along
It is converted to the active form by Ghrelin O-Acyltransferase (GOAT)
It is high in the morning and then goes down after breakfast and rises again until lunch (it drops after every meal and then slowly rises)
How does ghrelin have its effects?
INCREASES appetite by directly modulating neurones in the arcuate nucleus:
STIMULATES Agrp/NPY neurones
INHIBITS POMC neurones
Ghrelin increases food intake in humans
