Samenvatting Physiology - Metabolism

Physiology notes

Energy balance
Intake: eating, absorption
Expenditure: basal metabolic rate, thermogenesis, physical activity

Voluntary food choice of children below the age 5 years is remarkably like
the official advice of the WHO for a healthy diet: parents influence the
children’s diet.

Energy balance is under homeostatic control.
The dual centre hypothesis:
VMH: satiety. If the VMH is lesioned  extreme hunger  obesity
LHA: hunger. If the LHA is lesioned  no hunger  anorexia nervosa

Body composition
 60% total mass = water
 1 kg carbohydrates
o 100-gram liver glycogen
o 300-gram muscle glycogen
 15% fat
o Varies from 5%-15% body weight
o 1 kg body function (cell membranes)
o Rest: energy stores
 10% proteins (amino acids)
o Muscle
Majority energy in the blood circulating is glucose.
Majority stored in tissues is fat and proteins.

Brain is dependent on glucose.
FFA  long term exercise or fasting
Amino acids  famine  break down of muscle protein
Glucostatic theory:
- Maintenance of glucose availability is crucial for life because glucose
is the most important energy substrate for the
brain
- Glucose sensors in the hypothalamus
Lipostatic theory:
- The amount of fat is regulated = maintenance
of the body’s energy stores
- Leptin signalling system


Mechanosensors (stretch receptors) in the stomach  afferent neurons in
the vagus nervus  satiation

Cholecystokinin (CCK) as well secreted in stomach as the liver.
- Stimulates secretion of the exocrine and endocrine pancreas
- Stimulates pepsinogen secretion

, - Inhibits HCl-secretion
- Causes gallbladder contraction
- Trophic effect on the pancreas
- Inhibits gastric emptying
- Has a satiety effect
Enterostatin: reduces fat intake
Ghrelin: only hormone that does not inhibit food intake. A meal inhibits
ghrelin levels. Short term increaser.
All factors from the gut go through the vagus nervus to the brain stem and
then project on the hypothalamus.

Obob (obese obese) mice are leptin deficient (produced by the fat tissue).
Leptin reduces food intake.
- These mice are 3 times normal weight.
- Homozygous for a mutant gene ob
Dbd (diabetic diabetic) mice are leptin receptor deficient. Leptin does not
get to the brain. Information that there is no fat available.

Leptin in fat mass. Long term signals go via leptin to the hypothalamus.
When leptin goes up, the brain makes the food intake reduce and the
energy expenditure and metabolism increase.

Leptin: a negative feedback fat signal
- Hormone released by fat cells
- Leptin receptors found in the brain
Leptin signalling system in the brain: melanocortin and NPY.
NPY increases food intake.
Blockage of alpha-MSH receptors  less pigmentation in skin and hair
and influences feeding behaviour.
Blockage of POMC receptor  obese, red haired.
Alpha-MSH is a satiety hormone.
- Leptin increases synthesis of alpha-MSH.
- Alpha-MSH is released by a POMC neuron through splicing.
Short term signalling comes from the liver, long term from fat mass
(leptin)
Arcuate nucleus (ARC) is below the VMH and LH, so on the bottom of the
hypothalamus.  leakage in the blood brain area  allows leptin to act on
the receptors.

Alpha-MSH = a satiety factor
FI= food intake.
NPY = hunger signal
Leptin reduces NPY  FI smaller.

AgRP is colocalized in the same neuron as
NPY and are released together at the same
time. If you stain AgRP and NPY both
colours light up in the neuron  mix of
both.
AgRP = a neuropeptide.