146. Appetite Regulation, Energy Expenditure

Question 1

Define and describe how much each of the following take up total daily energy expenditures.

1. Resting Metabolic Rate (RMR)
2. Thermic Effect of Food (TEF)
3. Physical Activity Level (PAL)

Answer 1

RMR: 65% TEE, energy to keep you alive
TEF: ~10% TEE, energy to digest/absorb food
PAL: 25% TEE, voluntary movement/posture/spontaneous activity

Question 2

What gut hormones are involved in appetite? How?

How do these adapt following weight loss?

Answer 2

Proximal Intestine: K Cells - GIP; I Cells - CCK
Distal Intestine/Colon: L Cells - GLP1/2, PYY
GLP-1, CCK, PYY signal satiety and decrease feeding (ANOREXIGENIC)

Ghrelin: only OREXIGENIC - NT in ARC and periventricular area of hypothalamus
levels increase before meals, decrease after meals
cause: increase food intake, increase body weight, decrease fat utilization (in rodents)
high baseline in pt with anorexia nervosa/diet induced weight loss

Weight Loss:
Higher ghrelin from baseline for weeks in response to weight loss = hard to keep weight off (levels higher, do not fall as quickly after meal)
Lower CCK, PYY from baseline = pt never feels full
Causes increased hunger and desire to eat following weight loss

Question 3

Leptin

• what is it, when is it secreted, where are receptors
• females vs. males
• effects
• congenital leptin deficiency sx
• effect of obesity on leptin
• adaptation to weight loss

Answer 3

Long-term signals in body fat sense energy stores, pulsatile diurnal secretion from adipose tissues to receptors in ARC/hypothalamus
females: higher leptin levels due to higher body fat % at same BMI as males - brains adapt to see higher leptin levels as normal (hypothalamus regulates it differently than males) - high variability in level among people of same gender/BMI
Effect: sense amounts of body fat - low levels cause increase food intake, decrease in EE (reproductive function - brain needs to sense enough energy to support a child - why anorexics lose periods)
CLD: no leptin = oversignal drive to eat and low EE (tx with leptin therapy - results in fat loss)
Obesity: Leptin resistance - leptin CNS receptor saturates - even as leptin levels rise with BMI, body does not sense enough leptin in CNS to stop eating
Weight loss: leptin levels remain below baseline = causing appetite stim (brain wants to eat more)

Question 4

What neuron populations in CNS are orexigenic and anorexigenic?
How does leptin affect these neuron populations?

What is Hypothalamic Obesity?
What is hypothalamic response to high fat diet?

Answer 4

Orexigenic: NPY, AgRP (release GABA)
Anorexigenic: POMC, CART
Baseline: Orexigenic signals “ON” to inhibit anorexigenic neurons
Neurons mediated by gut peptides + leptin
Leptin: inhibits NPY/AgRP (disinhibits POMC/CART) - low leptin levels have greater modulation than higher levels

Hypothalamic Obesity: damage to hypothalamus - abrupt onset, rapidly accelerating weight gain (tumor, trauma, surgery, aneurysm, radiation)

High Fat Diet: neuron damage/inflammation = more resistance to AgRP/NPY and POMC/CART neurons = less response to leptin in hypothalamus

Question 5

What to do with child with severe obesity?

What non-homeostatic ways is eating regulated by?

Answer 5

Severe obesity = screen for genetic mutations (MC4 receptor - in POMC/CART signaling) or leptin receptor mutation - if deficient give leptin supplement

Reward pathways: other stimuli determine what/how much we eat (sensory factors, cognitive factors, enviro, lifestyle)
Look at food = increase activity of amygdala, medial olfactory cortex = increase hunger, decrease fullness = huge effect to increase appetite
Reward pathway overrides homeostatic pathway