Monday, March 12, 2018

PEEK 13/ 2nd edition THE CHRONIC DISEASE OF OBESITY





Chapter 5:  The Science of Obesity


Insulin is probably one of the main reasons people gain their weight
back from the plateau of weight loss.


Let me go through the physiology.


Insulin peripherally is anabolic.
It promotes constructive metabolism.
Insulin will store fat in adipose and glycogen in muscle and liver.


Insulin centrally is catabolic. (like Leptin)
Insulin breaks down molecules to release energy..


Low Leptin increases food intake and suppresses energy expenditure.
"Leptin is an important signal for starvation."


High Leptin reduces food intake by inhibiting NPY/AgRP neurons
and stimulating the alpha-MSH neurons.
(Except in the Obese who become Leptin resistant.
Only lean individuals appear to be regulating body weight.)


Centrally, Leptin and Insulin
share same feeding inhibitory and thermogenic pathways.


However, in Obese, Insulin triggers steroidogenic factor 1 (SF-1)
expressing neurons of the VMH, resulting in inhibition of POMC neurons,
which promotes food intake and perpetuates obesity.


Let me repeat.
1-In lean individuals who have never been obese,
leptin and insulin prevent them from becoming obese.
Centrally high levels of leptin and insulin
reduce food intake and suppress energy expenditure through same pathway.
 Centrally both insulin and leptin are catabolic.
A lean individual eats a large meal.  
High insulin from pancreas peripherally stores fat and adipose
and centrally increases thermogenesis to burn excess calories to maintain weight.


2-A “genetically obese prone” individual with early insulin resistance
and early leptin resistance does all this less effectively.  
Storing more fat, burning less energy and allowing more food intake
on the slippery slope of always more appetite
and more fat with more leptin and insulin resistance.
With tremendous will power an obese person follows the 3500 calorie rule
and is able to lose weight for 6-9 months until the plateau is reached.  
At this point the thermodynamic laws of physics fail
and the biological laws of survival take over.
Your body thinks you are starving.
 The plethora of retained fat cells in the reduced obese tell the brain this early warning.
The numerous fat cells did not disappear, they are shrunken.
 The subsequent low leptin level in the face of so many fat cells signals the body
that starvation is occurring by sending out MiRNA’s to many cells all over the body.  


This is the Sponge Syndrome.  
So many fat cells remain in the reduced obese, so little leptin.
 Insulin probably high, but there is resistance to it’s glucose lowering effect.
MiRNA’s(episomes) are sent from the billions of fat cells to all the body via blood stream.


Priority number one for the body is no longer to heat the body
in order to restore the prior size of the fat cells(get back to prior high level of Leptin).  
Thermogenesis is reduced in the plateau
as the determined dieter goes to 800 calories a day or
increases to three hours of walking a day.
The physics of the 3500 rule calorie fails.
This is where the dieter learns
that most of calories burned during 24 hours are from the resting metabolism.
 Up to 70% of calories  may be burned by the
brain, liver, kidneys, heart, lungs, endocrine organs.  
Muscles themselves become food at this point, not the tool for a weight lifter to lose weight.  
Thermogenesis is reduced by Leptin and Insulin
and I suspect MiRNA
(by sending the message of starvation to the many cells of the body)
The dieter can do nothing about this.
Maybe the new diet pills and gastric bypass help?


Introducing Ghrelin.
The only hormone that stimulates appetite?
Leptin inhibits Ghrelin but not in obese.
Insulin inhibits Ghrelin centrally but not in obese.
The reduced obese with the billions of excess shrunken fat cells and
subsequent low leptin level have high Ghrelin levels
making us thinking of nothing but our next meal.
The sub-starvation state.
 This miserable psychological condition is what most diet guidelines
are telling us we must stay in to maintain our weight loss and they are wrong.
It is not sustainable.
The high insulin levels will take any food we eat and use the food for fat storage.
 It might take years but at any moment of mild excess food intake above 1,000 calories,
those extras calories don’t go to build muscle or
make heat it  is used instead to store fat(increase Leptin level).
Survival of famine is the body’s main objective.  It’s in our DNA.
The sponge of excess fat cells with the help of insulin
will convert food to fat at low levels of calorie intake
to slowly get the leptin level back to a safe level for survival.
MiRNA also play a key role yet to be totally determined.


This is why you can’t maintain your weight loss.
This is why your plateau usually is not even close to your optimum BMI.
Your body uses your leptin level to determine your risk of starvation.
Your reduced obese body has the same number of fat cells
as your former maximum obese self
and all those excess shrunken fat cells secrete an excess of MiRNA.
The reduced obese body uses the excess adipocytes that is has
as a survival mechanism to rapidly re-gain fat and they never go away.
If you surgically remove them, they grow back some place else.
Brain cells die. Fat cells replace themselves as they are more important for survival.   


Obese individuals are Leptin resistant and often insulin resistant.
Thus Leptin and Insulin acts differently in the obese state.
They also act differently in the reduced obese state
which is why people cannot maintain their weight loss despite low calorie diet and exercise.


What is the truth about the failure of the reduced obese to maintain weight loss?
“The answer is that there is a
convergence of evidence from multiple lines of inquiry—”
Part of the anorexic pathway:
Leptin
Insulin
Ileal Brake controls rate at which food moves through the gut.
It is a form of gut traffic control.
Locaserin acitvates POMC neurons in brain.
Alpha MSH release
Part of the feeding stimulatory pathway
Ghrelin opposes Leptin effect in hypothalamus. Leptin inhibits ghrelin action.
Ghrelin activates NPY/AgRP neuron
Ghrelin stimulate NPY release and AgRP release increase orexigenic pathway.


The above is a short summary that is based in science and on my Obesity Boards.


Medications were designed to affect these pathways.  
The brain makes compensations with one medicine,
thus multiple medicines needed to affect many of the different pathways that cause weight regain.

1 comment:

  1. I read it Brian. I'll be away from three weeks (in Spain) shortly. If book arives before then, I'll read it there! If afterwards., I'll read it when I get back. I'm still keeping the weight off. Almost 4y at target weight. I was last my longterm weight almost 6y ago. That's when I first gave up sugary stuff.

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