Reglation Of Body Weight Flashcards
Leptin
Lep thin = satiety
= body weight focused
=adipose shrinking / growing modifies level of leptin
Produced by adipose tissues
Ob/ob
Obese
Deficient in ligand leptin
Always hungry
Insulin resistant
High blood glucose bc can’t stop eating
Db/db
Diabetic
Obese
Lacks receptor for leptin
Primary location of leptin receptor
Hypothalamus
- neurons of arcuate nucleus
What regulates ampk?
Ratio of amp to atp
Leptin
Adiponcerin
Ucp1 direction of H+
Into matrix
Organism level hormones for E balance
Leptin = energy use
Insulin = energy storage
Cellular level E balance regulation
Amp/atp to AMPK
FA derivatives to PPARs
Pathway for leptin
Leptin from adipose to hypothalamus
Hypothalamus releases Norepinephrine = fight or flight = GLPC protein called B3AR
= g alpha activated - AC - cAMP increases
PKA activated
= MAPCK activated
= ucp1 transcription goes up
Also pka = periliptin phosphorylated = lipases can breakdown TAGs = FFAs to mitochondria
= UCP1 gene enables oxidation of atp via thermogenesis = no atp released, heat instead
Want to get rid of body energy as heat
Want to break down fat = size of adipose to be maintained
Signals from neuron that have info about hunger
NPY = eat = neuropeptide Y
Alpha - MSH = don’t eat
Leptin —> neuron signals
Inhibits NPY
Activates alpha MSH
Insulin —> neuron signal
Inactivated NPY
Insulin is from pancreas
GLP1 —> neuron signal
Inactivates NPY
From gut
Ghrelin
Activates NPY
From Stomach
Adiponectin
From adipose tissue
Increases sensitivity to insulin
Activates FA uptake and rate of beta oxidation
Can activate AMPK ?
Adenylate kinase reaction
ATP + AMP —> 2ADP
Amp activates AMPK
ATP inactivates ampk
AMPK details
Key kinase protein
Activates catabolism processes = atp production
Inactivates anabolism = synthesis, transport, muscle contraction, growth
Leptin interaction with ampk
In hypothalamus = ampk promotes feeding behavior = promotes atp production = limits atp consumption, increase other energy production
leptin inhibits ampk = appetite suppression by inactivating NYP and activating alpha MSG = we do not need to break things down
= we are fueled and we need to use the fuel to build things
This in turn decreases atp in tissues = amp:atp increases = eventual activation of ampk in peripheral tissues
In peripheral tissues : leptin leads to norep being releases = PKA pathways, TAG breakdown
== beta oxidation = no atp production = ratio is not improved for ampk
Kinase for AMPK
LKB1
= liver kinase protein B
What raises amp to atp ratio?
Chemical and physical work
ATP —> adp + pi = synthesis / motors
ATP —> amp + PPi = FA, amino acid activation
What processes can totally mess up atp production?
Hypoxia, glucose starvation, certain poisons
ACC and AMPK
ACC = acetyl coA Carboxylase = produces malonyl coa = first step to FAS
= liver/ white adipose tissue
-> malonyl coa inhibits carnitive Acyl transferase = 1st step to FA breakdown in mitochondria
AMPK inhibits ACC
When you are hungry, body wants to
When you are full, body want to
Break down materials (for e)
Build materials (using e)
Mechanisms of hormone action
G protein coupled receptor
Receptor enzyme = thyrosine kinase
Gated ion channel
Nuclear receptor
PPAR details
Peroxisome proliferator activates receptors
Act in liver, muscle, adipose tissues
Respond to changes in dietary lipids
Alter gene expression for fat/ carbs metabolism
Ligands for PPARs
FAs and FA derivatives
What enables PPAR to regulate rate of transcription for target genes?
Binds to its Ligand
Now it is able to bind to RXR = heterodimer
RXR has separate ligand = 9cisretinoic acid
Binds to DNA regions of interest
See vitamin d3 example and VDR later on
PYY details
Acts on Same GPCR site as GLP1 - both from gut
Glucagon like peptide receptor = all over the body = pancreas
= gpcr patwhays - galpha for sure = PKA = calcium up and insulin secretion up
= signal to inactivate NYP neuron = hunger down
Glucagon signals what
Hormonal signal from pancreas alpha cells
Blood glucose levels too low!
Opposite effects of glucose in blood
Need to release glucose
Counters insulin effects = glucose uptake when blood sugar is high
Through what pathway does glucagon send signals?
GPCR
Specifically alpha protein
= same as epinephrine = camp up so PKA up so glucose released
= fight or flight = need energy fast = glucose in blood needed
Is PKA not involved in insulin signaling?
No
Only g protein signaling pathways
Insulin = PI3K pathway = PKB involved
MAPK pathway = raf1, mek, Erk involved
Thiazolidine and PPARs
TZD is agonist for PPAR gamma
Stimulates genes for insulin sensitivity
Glucose uptake
Glycogen synthesis
Leptin receptor pathway
1 leptin molecule
2x receptor molecules
Each with once JAK
Autophosphorylate JAK = leptin receptor is phosphorylated
Activated
Phosphorylates STAT = 1 per JAK
2x STAT dimerize
= genes for appetite control
= POMC transcription
POMC is precursor for
Alpha MSH
Leptin pathway memory
Lip thin
Get jacked stat = each arm needs to be buff = 2x Jak and stat
