Obesity and the endocrine control of food intake Flashcards
what is the name of the key area involved in the regulation of food intake?
arcuate nucleus
what allows the arcuate nucleus to carry out its function
Incomplete blood brain barrier, allows access to peripheral hormones.
It’s a circumventricular organ.
Integrates peripheral and central feeding signals.
what are the two neuronal populations in the arcuate nucleus and what do they do?
Stimulatory (NPY/Agrp neuron). INCREASE APPETITE
Inhibitory (POMC neuron): DECREASE APPETITE
both sets of neurons extend to other hypothalamic and extra-hypothalamic regions
what are potential human 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 are the characteristics of the ob/ob mouse?
Recessive mutation. • Profoundly obese. • Diabetic. • Infertile. • Stunted linear growth. • Decreased body temperature. • Decreased energy expenditure. • Decreased immune function.
Similar abnormalities to starved animals.
what is leptin?
Discovered in 1994. •Codes for 167 amino acid hormone
•Missing in the ob/ob mouse.
-decreases appetite
what does leptin do?
Low when low body fat High when high body fat
•Central or peripheral administration decreases food intake and increases thermogenesis.
•Activates POMC and inhibits NPY/AgRP neurons.
why is leptin ineffective as a weight control drug?
Leptin circulates in plasma in concentrations proportional to fat mass.
• Most fat humans have high leptin.
• Obesity due to leptin resistance hormone is present but doesn’t signal effectively.
what other effects can leptin lead to?
Absence of leptin has profound effects, including hyperphagia, lowered energy expenditure, sterility.
However, leptin is an anti-starvation hormone rather than anti-obesity hormone.
Presence of leptin tells the brain that one has sufficient fat reserves for normal functioningbut high leptin has little effect
where are the leptin receptors?
hypothalamus
how many different hormones does the gut release?
The gastrointestinal tract is the body’s largest endocrine organ. • Releases more than 20 different regulatory peptide hormones. • Influence processes including gut motility, secretion of other hormones, appetite. • Release regulated by gut nutrient content.
what is ghrelin?
what does it modulate?
28aa gastric hormone
activated by Ghrelin O-acyltransferase ‘GOAT’, adding a fatty acid chain to its third aa
- Stimulates NPY/Agrp neurons.
- Inhibits POMC neurons.
- Increases appetite
what cells secrete PYY and GLP-1
L-cells
what does PYY do?
Inhibits NPY release.
• Stimulates POMC neurons.
• Decreases appetite.
what is GLP-1?
Glucagon-like peptide-1
Gut hormone coded for by the preproglucagon gene and released post-prandially.
Well characterised incretin role in stimulating glucose-stimulated insulin release and also reduces food intake
What is saxenda?
Long-acting glucagon-like peptide-1 receptor agonist (liraglutide) from Novo Nordisk.
Double the dose used for T2DM. Approved by FDA in 2014 and EMEA in 2015
gut hormones: what are the three types of satiety action?
Post-prandial Reduces food intake following a meal
Chronic Gut disease – chronic elevation suppresses appetite
Acute nausea Toxin ingestion – acutely very high levels
what comorbidities are associated with obesity?
depression sleep apnoea bowel cancer peripheral vascular disease gout MI stroke hypertension diabetes
what is the thrifty gene hypothesis?
- Specific genes selected for to increase metabolic efficiency and fat storage. In the context of plentiful food and little exercise these genes predispose their carriers to obesity and diabetes
- Evolutionarily sensible to put on weight.
- Thin humans didn’t survive famines, so didn’t pass their genes on to modern humans
what is the adaptive drift hypothesis?
Normal distribution of body weight: the fat are eaten, the thin starve.
• 10-20K yrs ago, humans learned to defend against predators.
• Thus obesity not selected against.
• Putting on body fat then a neutral change (genetic drift). (though unlikely to put on much weight).
• In current context, the inheritors of these genes become obese.
