Leptin and Adiponectin Flashcards
what is the only adipokine to decrease with obesity
adiponectin
what does the co-culture experiment show
Co-incubation study = incubate 2 cell types together
- Muscle cells, culture and grow it (from rectus abdominis)
- Fat depot is mammary = from breast (representative depot of visceral fat) more realistic compared to going deep to get the viscera
- Let mix and make contact or make layers with a fine screen between, stopping physical mending - If they coincubation, after 48hrs if you then isolate muscle cells and give an insulin challenges, and look you see impairment
two ways that fat cells increase
hypertrophy or new cells
what way is worse increase size or quantity
size
why is an increase in visceral adipose cell size bad
we hit a threshold due to certain size and we create a stress response sending out cytokines and peptides that recruit immune cells (macrophages)
what do the macrophages change (altered secretory profile)
Pro-inflammatory response
- increased TNF, resistin, IL6, IL8 and FA
- decrease in adiponectin
Causes problems with insulin response over all and now the muscle is unable to clear glucose
what do toll like receptors do
triggers immune response when FA bind
what did the removal of VF but not subcutaneous fat from aging/diabetic rats show
as the rats aged they became more insulin resistant
- VF removal saw an increase in glucose clearance similar to that of caloric restriction
- sub-Q fat removal was only similar to the sham group (less than young)
what is lipoatrophy
absence of peripheral adipose tissue
- associated with severe insulin reisstance
why is the absence of peripheral adipose tissue a bad thing
we are still consuming fat so it is converted and then needs to be stored which is in tissue instead like heart and liver
what does the study done where they transplanted AT from either a normal or leptin deficient mouse into a lipoatrophic mouse show
lipoatrophic mice = elevated bld glucose, insulin, TG-insulin resistant, liver TG
Transplanted with wildtype AT = improvement (decrease in all and more insulin sensitive)
Transplanted with no leptin = no improvement
leptin =
the anti obesity hormone
t or f leptin has both central and peripheral effects
true
what positive correlations does leptin have
positive correlation to adiposity and BMI
what are the central effects of leptin
decrease NPY and appetite
increase SNS activity
leptin stimulates
FA oxidation in muscle
how does leptin increase FA oxidation
activates AMPK
- AMPK detects the disturbance in energy charge (increase ATP)
what happens when AMPK is activated
ACC produces malonyl CoA
- puts a break on the carnitine system
- malonyl CoA is an inhibitor of this
= AMPK deactivates this so there is less malonyl CoA = less of a break = more fat in
the important peripheral role of leptin is to prevent
lipotoxicity in non-adipocytes
- increase AMPK and PGC1a = increases FA oxidation and mitochondrial content
what does an increase in HSL (ERK) and lipolysis do to lipid content
decreases it
(leptin turns on the HSL = fat breakdown)
how does leptin correct a HF diet (insulin resistance)
leptin increases insulin stimulated glucose uptake
- increases IRS-1, insulin stimulated PI3Kinase activity, Akt phosphorylation, plasma membrane and total GLUT4
decreases = muscle lipid content (TG, DAG, ceramides)
how is adiponectin related to obesity and insulin resistance
inversely
adiponectin functions much like leptin as it increases
AMPK/FA oxidation
mitochondrial biogenesis
restores insulin stimulated glucose uptake in HF fed rodents
Adiponectin gene therapy ____ mice from a HF High sucrose diet
protects
- improves glucose tolerance and lose fat mass
skeletal muscle becomes _____ to the ability of leptin and adiponectin to stimulate FA oxidation
resistant
(observed in obese humans)
is leptin and adiponectin resistance inducible and how
yes via HF diets (modifiable by lifestyle)
what does early leptin/Ad resistance do
decrease fat oxidation/increase storage
and insulin resistance
when do we first observe Ad resistance in a mouse HF diet
only 3 days in
when are Plasma membrane FA transporters increased in a HF diet in mice
2 weeks
when are reactive muscle lipids increased in a HF diet in mice
by 2 weeks
when do we see a decrease in insulin response in a HF diet
between 2-4 weeks
does Ad and leptin resistance occur slowly or rapidly
and before or after impaired insulin response
occurs rapidly and prior to
how can you prevent Lep/Ad resistance
via diet and exercise
- treadmill training prevents leptin resistance
- fish oil supplementation prevents diet induced leptin and Ad resistance in muscle
Does an improvement in leptin and Ad response precede improvements in muscle insulin response
we see restoration of FA oxidation response and improvement of insulin response following
what does the study show in the trying to reverse leptin resistance (HF diet + 4 weeks treadmill maintaining diet)
insulin response recovers with 1 week of exercise
- this corresponds to a decrease in muscle ceramide content
leptin response was restored AFTER the reduction in muscle lipids and improved insulin response
Restoration of adiponectin response
we have failed to see this through 2 weeks of exercise or fish oil supplementation even though those DO reverse insulin resistance
explain how FFA are related to inflammation
JNK SOCS3
TLR4
IkKB and NFkB increasing in nucleus
_____ signs of inflammation after 3d of HF feeding
No
what happened when aspirin was given as a supplementation with the HF diet
it didn’t prevent anything (decrease inflammation if that was the cause) it actually reduced adiponectin response
Adiponectin and leptin resistance are neither _________ prior to the recovery of insulin response
REVERSABLE
what was the hypothesis that said leptin and Ad resistance was
PROTECTIVE
how would Lep and Ad be protective
prevent lipid overload into teh mitochondria
deportonated FA
ROS production
how long does it take for the increase of ROS production due to excessive FA in MITO
little as 3 days on HF diet
what do ROS activate
stress kinases and impairs insulin signalling
the hypothesis for ROS production and ad/lep resistance
ROS production impairs the ability of Leptin and Ad to stimulate mitochondrial FA uptake and oxidation
what did they use for the study design to prove their new hypothesis
used a control diet plus antioxidant (N-acetylcysteine)
and HF diet
and HF diet + N-a
what is glutathione (GSH)
a cellular redox buffer = index of the oxidative state (GSSG = oxidized GSH)
HF diet _____ oxidative state in oxidative muscle
increases
what findings were seen in the soleus with the inclusion of antioxidant
does not protect against HF diet induced Ad resistance
what findings were seen in the EDL with antioxidant
Ad resistance develops with a HF diet even though oxidative status was unaffected
do ROS acutely/directly impair Ad-stimulated FA oxidation
no H2O2 doesn’t impair the ability of Ad to stimulate FA oxidation
= hypothesis = wrong
