Adipocytes Energy Balance 1 Flashcards
White Adipocytes (WATs)
Take in and release FA
Take in FA from any plasma fat source
Where does Glycerol 3 Phosphate come from?
Glucose or Fructose ==> DHAP ==> Glycerol 3 Phosphate ==> Triaglycerol synthesis
Adipose tissue in adult humans is mostly WAT, whose job is to store FA.
Insulin stimulates FA storage in WAT, by increasing FA (LPL) and glucose (GLUT4) entry.
Insulin inhibits FA release from WAT by inhibiting lipase (HSL and ATGL) activity and
perilipin phosphorylation.
- Both FA and glycerol released from WAT can be used for energy
- Triglycerides stored in other places:
a) muscle
b) liver
Health consequences of these stores will be discussed later.
WAT is an endocrine organ! Discussed later.
BAT is thermogenic, due to uncoupling proteins in the mitochondrial inner membrane.
Adipose tissue in adult humans is mostly WAT, whose job is to store FA.
Insulin stimulates FA storage in WAT, by increasing FA (LPL) and glucose (GLUT4) entry.
Insulin inhibits FA release from WAT by inhibiting lipase (HSL and ATGL) activity and
perilipin phosphorylation.
- Both FA and glycerol released from WAT can be used for energy
- Triglycerides stored in other places:
a) muscle
b) liver
Health consequences of these stores will be discussed later.
WAT is an endocrine organ! Discussed later.
BAT is thermogenic, due to uncoupling proteins in the mitochondrial inner membrane.
Low insulin effects on... Glut 4 ATGL/HSL ACC in sum...
- Glut 4: low and lower glucose uptake
- ATGL/HSL: high on adipocytes ==> release FA into blood
- ACC==> low and low malonyl CoA ==> higher CAT I in liver and muscle ==> higher FA oxidation
- in sum ==> favors FA oxidation
Arcuate Nucleus... which stimulate and which suppress appetite... What do each respond to... POMC? NPY?
POMC are anorexigenic and respond to glucose levels
NPY are orexigenic and respond to low FA levels.
NPY inhibits POMC
What are the important transporters on pancreas with regard to insulin release?
GLUT 2
ATP-inhibited K channel
Ca voltage gated channel
Insulin containing vessicle
What happens when glucose enters pancreas beta cells?
hexokinase (saturates fast) ==> ATP
ATP-inhibited K channel is blocked ==> K stays in cell ==> depolarizes cell ==> Ca enters cell ==> insulin is released
How glucose affect the POMC neuron?
Glucose ==> GLUT 2 ==> ATP ==> ATP-inhibited K channel ==> depolarizes cell ==> cell fires ==> cell is an inhibitory cell that inhibits appetite
(Note: these cells might also be stimulated by lactate from Astrocyte glycogen stores)
Astrocytes store glycogen
Astrocytes
how is ACC regulated…
Insulin?
Glucagon and Epi?
Gluca and Epi ==> cAMP ==> PKA ==> ACC ==> malonyl CoA inhibits CAT I
Insulin ==> PDE inhibits cAMP
How is NPY regulated?
Note: NPY is orexigenic.
ACC
FAS
CAT I
AMPK
explain NPY orexigenic vs anorexigenic... ACC? FAS? CAT I? AMPK?
ACC is anorexigenic
FAS is orexigenic
CAT I is orexigenic
AMPK is orexigenic
In class... ACC inhibition is orexigenic FAS inhibition is anorexigenic CAT I inhibition is anorexigenic AMPK activation is orexigenic (causes ACC inhibition)
AMPK inhibits ACC.
ACC inhibits CAT I (via producing Malonyl CoA)
Malonyl CoA activates FAS.
In the brain, FAS is stimulated only when overall energy stores are low.
From Higgs: In a global sense, your logic is good but backwards in a way. FA are high in the blood in periods of low food in-take. This is because FA are released from adipocytes in times of fasting. So, FA in the blood (and cerebro-spinal fluid) would be a sign that it might be time to eat.
This is opposed to TG in the blood, either in VLDL particles or chylomicrons. Both are signs of plenty (VLDL is coming from the liver, and is high when there is excess glucose, that the liver has used to synthesize FA then packaged up as TG in VLDL. Chylomicrons are derived from dietary FA).
The statement I made that FAS inhibition is anorexigenic is pretty confusing and I regret making it (although it is true). Here’s the logic. FAS depletes the pool of malonyl-CoA. High malonyl-CoA is inhibiting CAT-1 activity in NPY neurons, thus is an anorexigenic signal. Inhibiting FAS causes less depletion of malonyl-CoA, thus is anorexigenic. The confusing thing here is that flipping the argument on its head (FAS activity is orexigenic) doesn’t really work.
For ACC, you have that one backwards. ACC is activated in times of plenty, because it’s part of the FA synthesis pathway (you only synthesize FA in times of plenty)
From Lynn: Basically, with Low ATP, ACC is inhibited, which stimulates CAT I. Both states are orexigenic.
When ACC is inhibited there is no malonyl coA produced so the body thinks there is no FA so it stimulates appetite.
When FAS is inhibited, malonyl coA backs up and increases which inhibits CAT-1 which tells the body there is lots of FA around and decreases appetite (this is same as CAT-1 Inhibition essentially).
AMPK causes ACC inhibition so again the body thinks there isn’t a lot of FA around so it stimulates appetite.
I think the part of FAS inhibition is more conceptual and you just need to realize that if malonyl coA increased because the downstream pathway was blocked you would get CAT-1 Inhibition (ACC is still working though thats why you get increased malonyl coA).
From Spencer: FAs stimulate appetite (via NPY neurons). ACC inhibition is orexigenic because you end up with less malonyl CoA, so increased fatty acid oxidation occurs (via CAT-1). I don’t know how this effects actual levels of FA since they are also being mobilized from adipose tissue, but fatty acid oxidation and hunger are on the same axis. FAS inhibition is anorexigenic because this is downstream of ACC, so you end up with a buildup of malonyl CoA, which inhibits CAT-1. This is a little counterintuitive since ACC and FAS are in the same axis, but Dr. Higgs said that the FAS inhibition effect is a little bit of a stretch.
Also, it seems counterintuitive that FAs stimulate appetite (since they’re basically energy floating around in the blood), but this does make sense because they’ve been released from adipose tissue in response to the conditions (ie low insulin, low food, adrenaline, etc).
What makes Leptin?
What is leptin production proportional to?
adipocytes produce leptin in proportion to the number and size of adipocytes
What is the effect of Leptin on…
POMC?
NPY?
Leptin stimulates POMC and decreases appetite (POMC is an appetite inhibitor)
Leptin inhibits NPY and decreases appetite (NPY is an appetite stimulator)
How does leptin affect brain wiring?
Long term leptin affects brain rewiring and can realign the “set point” of weight for increased weight.
