L6 - Hypothalamic Energy Control Flashcards
Experiment showed hypothalamus role in energy control
lesions in rodents
Lesion of VMN
hyperphagia
Aphagia
lack of eating
Lesions of lateral hypothalamus
aphagia
Adiposity signals
hormonal = insulin and leptin
Insulin & leptin act on?
arcuate nucleus
How do hormones reach the hypothalamus
through tanycytes
key neurons in Arcuate nucleus are
antagonistic
Neurons in Arcuate nucelus
NPY and POMC
NPY
neuropeptide
POMC
neurohormone
NPY function
stimulates food intake reduces energy expenditure
POMC function
reduce food intake
increase energy expenditure
POMC neuron release
a-melanocyte stimulating hormone
NPY inhibits
PVN
NPY stimulates
LHA
PVN action
net catabolic
LHA release
two neuropeptides
orexin A
melanin concentrating hormone
ISLET1
key transcription factor
ISLET1 function
determines identity of hypothalamic POMC neurons
ISLET1 predicts
POMC expression
ISLET1 predicts POMC - experiment
immunohistochemistry, transgenic reporter line
ISLET1 homeobinding DNA motifs
nPE1
nPE2
Model generated for ISLET1/POMC neuron
conditional KO mouse
Key features of conditional KO mouse
cret2, tamoxifen, loxP, cre recombinase
ISL1 KO model
POMC neurons fail to differentiate, early onset obesity
Hypothalamic development model
sequential ansiotropic growth
FGF10+ stem cell progenitors give rise to
ISLET1 progenitors
type 2 diabetes
loss of neuron & function