Obesity and the Endocrine Control of Food Intake Flashcards
Where in the Brain is food intake regulated - SPECIFIC
Hypothalamus ARCUATE NUCLEUS
What ables the ARCUATE NUCLEUS to regulate food intake
circumventricular region)- allows access to peripheral hormones
2 neuronal populations in the arcuate nucleus?
Stimulatory (NPY/Agrp neuron)
Inhibitory (POMC neuron)
Inhibitory neuronal population in the arcuate nucleus?
POMC neurons
Stimulatory neuronal population in the arcuate nucleus?
NPY/Agrp neuron)
What hormonal inputs regulate food intake (3)
ghrelin, PYY, and normal leptin
What neuronal input regulates food intake
Vagus
Hormones of the arcuate nucleus? (2)
Agrp and POMC
What stimulates hunger
You trigger hunger by the release of Agrp from the arcuate nucleus which is an endogenous antagonist of MC4R, this blocks the inhibitory signal of α-‐MSH and stimulates food intake
What receptor controls hunger in the PVN
MC4R
MC4R receptor is important in
hunger
Why aren’t you hungry all the time
Under normal conditions, the POMC will be broken down to α‐MSH which is an endogenous agonist of the MC4R, which suppresses food intake
MC4R stimulation impact on food intake?
Decreased
MC4R inhibition impact on food intake?
Increased
MC4R inhibitor?
NPY/Agpr neurons
MC4R agonist?
Alpha-MSH
Alpha MSH is cleaved from
POMC
- No XXXXX mutations associated with appetite have been discovered
NPY/Agrp
- X deficiency and Y cause morbid obesity (X in the arcuate nucleus and y is PVN)
X POMC
Y MC4-R mutations
- OB GENE CODES FOR X
LEPTIN
What was observed in ob/ob mice (7)
- Obese
- Diabetic
- Infertile
- Stunted linear growth
- Decreased body temperature
- Decreased energy expenditure
- Decreased immune function
What was missing in ob/ob mice
Leptin
Where is leptin released from
white adipose tissue
Leptin levels when low body fat?
Low
Leptin levels when high body fat?
High
Physiological effect of leptin?
Inhibits feeding
Neuronal MoA of leptin?
- Activates POMC and inhibits NPY/Agrp neurons
- Leptin circulates in plasma concentrations proportional to XX
fat mass
Why is leptin ineffective as a weight loss pill?
Obese people tend to have leptin resistance
On who is leptin effective as a weight loss pill?
LEPTIN IS EFFECTIVE IN TREATING LEPTIN DEFICIENT CHILDREN AND ADULTS
How is leptin an anti-starvation hormone rather than an anti-obesity one
- Presence of leptin tells the brain that one has sufficient fat reserves, but it doesn’t stop you from wanting to eat
- Central administration of insulin of food intake?
- Central administration reduces food intake
Does insulin have receptors on the hypothalamus?
Yes
Central or peripheral administration of leptin will decrease X and increase Y
food intake
thermogenesis
Effect of leptin on puberty?
Lack of leptin means the hypothalamus doesn’t release GnRH
Ghrelin is activated from its inactive form by …
GHRELIN O-ACYLTRANSFERASE
Effect of ghrelin on arcuate nucleus neuronal populations?
- Stimulates NPY/Agrp neurons
- Inhibits POMC neurons
- Increases appetite
Ghrelin is secreted by…
The stomach
The stomach secretes what food intake controlling hormone
Ghrelin
What cells and where secrete PYY
enteroendocrine/L- cells in the distal small intestine and colon
What cells and where secrete GLP-1
enteroendocrine/L- cells in the distal small intestine and colon
enteroendocrine/L- cells in the distal small intestine and colon secrete what food intake controlling hormones (2)
PYY and GLP-1
Effect of PYY on arcuate nucleus neuronal populations?
- Inhibits NPY neurons
- Stimulates POMC neurons
Effect of ghrelin on food intake
Increases
Effect of PYY on food intake
Decreases appetite
Effect of GLP-1 on food intake?
reduces food intake (suppresses appetite)
GLP 1 stands for
Glucagon like peptide
When is GLP-1 released
Post prandially
When is PYY released
Post prandially
When is ghrelin released
High in morning, goes down after food and cycles
Effect of GLP-1? (2)
- Well characterised incretin role in stimulating glucose-stimulated insulin release and also reduces food intake (suppresses appetite)
What are GLP1 based drugs used to treat?
Diabetes mellitus
GLP1 in inactivated by … 1/2 life?
by DPP‐4 (dipeptidyl peptidase 4)
about a minute in circulation
What is Saxenda
Long‐acting GLP-1 receptor agonist
Example of a Long‐acting GLP-1 receptor agonist ?
Saxenda
Why is PYY not a good drug target?
Has a narrow therapeutic index.
If you inject someone with PYY, you will get a big, transient increase in drug concentration and then a relatively rapid drop
At high levels, it will cause nausea
There is a relatively small sweet spot in terms of drug concentration that gives the effects that you want
What is the thrifty gene hypothesis
Specific genes selected for to increase metabolic efficiency and fat storage- BUT in an environment with plentiful food and low exercise these genes predispose to obesity/diabetes
What is the adaptive drift (drifty gene) hypothesis?
- Normal distribution of body weight; the fat are eaten, the thin starve This was probably true for humans originally
- 10-20k yrs ago, humans learned to defend themselves
- Thus obesity wasn’t selected against
- Putting on body fat was then a neutral change (genetic drift)
- In current context, the inheritors of these genes become obese
