Few bioenergetic questions. Need your thoughts

[Kairo]

As I understand it, a healthy body cannot become obese, feedback mechanisms will reduce appetite with weight gain,
and only in stressful conditions and hunger of cells is obesity possible

Question 1
Is the body, being fat, trying to get rid of fat through the mechanisms of high adrenaline and insulin resistance?

Question 2
Why is the body being obese still has an appetite if it has to switch to fats due to high adrenaline. What can prevent a cell from processing fat into atp/energy

Question 3
If the body, even being fat, prefers glucose, why does the body become insulin resistant when overweight? after all, this prevents glucose from working

Question 4
Fat itself becomes an endocrine gland, and obesity is always a stress for the body? Or, theoretically, can there be a healthy person with obesity?

 

[Peatful]

Define: obese
Define: being fat
Define: overweight

 

[Kairo]

Define: obese
Define: being fat
Define: overweight

When you have so much fat in your body that it affects your metabolism/hormones. And independently becomes a stressful and inflammatory factor for the body
Probably

 

[Peatful]

I’m at work and this is voice recognition to text

So you’re using the terms interchangeably
And you’re already presuming that fat causes inflammation?

I was a terribly underfed underweight person, and I had plenty of inflammation going on. I was a metabolic and hormonal mess. Trust me.

Thyroid health is the answer for the skinny or the obese person
Mitochondrial respiration
Those are the foundations of metabolic health

 

[mostlylurking]

Question 1
Is the body, being fat, trying to get rid of fat through the mechanisms of high adrenaline and insulin resistance?

I doubt it. There's a problem with using sugar/glucose for energy (ATP). I'm personally familiar with thiamine deficiency derailing oxidative metabolism. During the time that my thiamine function was blocked (via Bactrim antibiotic), everything I ate (low fat milk and oranges mainly) was packed into storage as fat. I gained 25 pounds in 25 days.

"Insulin resistance"

Systemic Inflammatory Response: Thiamine and Magnesium Status (Sir TaM Study) | Clinical Research Trial Listing ( Inflammation | Iron Deficiency | Thiamine Deficiency | Magnesium Deficiency ) ( NCT03554668 )

Clinical trial for Inflammation | Iron Deficiency | Thiamine Deficiency | Magnesium Deficiency , Systemic Inflammatory Response: Thiamine and Magnesium Status (Sir TaM Study)

www.centerwatch.com

"Obesity is also associated with thiamine and magnesium depletion (17, 20, 26, 27). Magnesium deficiency is also associated with a CRP rise (28-30). Thiamine status is proven to affect lactate concentrations in the blood (2, 3). Lactate accumulation is known to precede the onset of insulin resistance and be characteristically found in patients with obesity related diabetes (31-37).

It is therefore possible that an underlying quiescent magnesium and / or thiamine deficiency may mediate insulin resistance. Thiamine, and its more lipid soluble derivative, benfothiamine, have already shown some promise in the treatment of diabetic complications."
-end paste-

Adrenaline is produced when blood sugar is low to trigger the liver to release more sugar from storage to be burned as fuel (to make ATP). However, if the cells are unable to utilize the blood sugar (that's there) because oxidative metabolism is blocked (via thiamine deficiency/functional blockage or hypothyroidism), this situation can be interpreted by the body to be the same as if the blood sugar is not available (=low blood sugar), so adrenaline can be triggered which results in even higher blood sugar that the mitochondria cannot use.

I've probably garbled this.
suggested reading:

Glycemia, starch, and sugar in context

Ray Peat

raypeat.com

Question 2
Why is the body being obese still has an appetite if it has to switch to fats due to high adrenaline. What can prevent a cell from processing fat into atp/energy

I think "appetite", or "hunger" is tied to the lack of production of ATP via oxidative metabolism. The cells get hungry for ATP (=energy). If there is something blocking the production of ATP (thiamine/magnesium deficiency, hypothyroidism), then hunger happens. High adrenaline is triggered via low blood sugar or the inability to burn glucose to make ATP. High adrenaline triggers the release of cortisol. Cortisol dissolves muscle for emergency fuel so you don't die.

Thiamine is also required to burn fat for energy; a thiamine deficiency/functional blockage would prevent a cell from processing fat into ATP/energy.

What Is Thiamine to Energy Metabolism? - Hormones Matter

Few people are aware that our lives depend on energy production and its efficient consumption.

www.hormonesmatter.com

Thiamine Deficiency and Aberrant Fat Metabolism: Clues to Adverse Reactions- Hormones Matter

Thiamine deficiency impacts mitochondrial functioning via multiple mechanisms. A new discovery shows just how important thiamine is to mitochondrial health.

www.hormonesmatter.com

Question 3
If the body, even being fat, prefers glucose, why does the body become insulin resistant when overweight? after all, this prevents glucose from working

I think that "insulin resistance" is the result of the inability of the body to use glucose for oxidative metabolism. Or, both of these things are the result of thiamine/magnesium deficiencies. Thiamine deficiency damages organs like the pancreas, liver, and thyroid. Insulin Resistance seems to encompass lots of things (multiple organs: pancreas, liver, etc.) and is a handy catch phrase for modern medicine.

High free fatty acids in the blood block the use of glucose for oxidative metabolism. Niacinamide supplementation can help keep free fatty acids lower so it is helpful.

suggested reading:

Glucose and sucrose for diabetes.

Diabetes was named for the excessive urination it causes, and for the sugar in the urine. It was called the sugar disease, and physicians were taught that sugar was the problem. Patients were ordered to avoid sweet foods, and in hospitals they were sometimes locked up to keep them from finding...

raypeat.com

"The antimetabolic and toxic effects of the polyunsaturated fatty acids can account for the "insulin resistance" that characterizes type-2 diabetes, but similar actions in the pancreatic beta-cells can impair or kill those cells, creating a deficiency of insulin, resembling type-1 diabetes.
The suppression of mitochondrial respiration causes increased free radical damage, and the presence of polyunsaturated fatty acids in the suppressed cell increases the rate of fat decomposition and production of toxins."

Question 4
Fat itself becomes an endocrine gland, and obesity is always a stress for the body? Or, theoretically, can there be a healthy person with obesity?

Toxins get stored in body fat. Polyunsaturated fatty acids (PUFA) are toxic and inflammatory. The body doesn't like to burn PUFA; it gets parked in the fat cells. Even the fat cells don't like to burn PUFA. As people age, the percentage of PUFA to saturated fats stored in the fat cells becomes more and more polyunsaturated, which equals to more and more toxicity and inflammation. Inflammation and estrogen are related. PUFA accumulation results in more inflamed and estrogenic fat cells.

suggested reading:

Ray Peat, PhD Quotes on Therapeutic Effects of Niacinamide – Functional Performance Systems (FPS)

Regeneration and degeneration - Types of inflammation change with aging

Older ways of understanding aging and degenerative disease are now returning to the foreground. The developmental interactions of the organism with its environment, and the interactions of its cells, tissues, and organs with each other, have again become the focus of biological aging research.

raypeat.com

 

[Kairo]

Thank you very much @mostlylurking

 

[mostlylurking]

Thank you very much @mostlylurking

you're welcome.

 

[Bioenergy_Space]

Your questions can be approached with two key concepts, free fatty acids (FFA) and the randle cycle. FFA in the blood refers to the amount of non esterified fat that can be used for beta-oxidation (the conversion of fat to energy). The randle cycle is the antagonistic relationship between glucose oxidation and beta-oxidation. They are inversely related

Obesity and insulin resistance, like all chronic diseases, is a state sustained by self-stabilizing positive feedback loops of stress systems. Now, beta-oxidation is stressful vs glucose oxidation because it generates 1/3 less CO2 and leaves the cell in a reduced state. Anytime you get increased beta-oxidation, the organism is in a stressed state. It responds by releasing adrenaline, cortisol and serotonin (roughly in that order). Because adrenaline is lipolytic it will further increase FFA in the blood, leading to a self perpetuating cycle. Cortisol chronically increases appetite (acutely it decreases it) and calorie partitions with a massive bias for adipose tissue. Serotonin will lower metabolism, leading to easier accumulation of excess calories.

Once the excess adipose tissue has been created, it will lead to chronically increased FFA, closing the loop. The FFA will "activate" the randle cycle and reduce glucose oxidation, lowering insulin sensitivity. Now the stressed state has been "written" into the tissues and endocrine state of the organism. You will need to intervene to stop the disease process.

The question is: what would lead to the initial increase in beta-oxidation that cascades towards obesity? Anything stressful really. Lack of sleep, excess PUFA, inflammation, low social status...

Two peaty concepts that are always important to keep in mind:

-Stress systems are always inefficient
-Positive feedback loops are central to degenerative diseases

 

[Jonk]

I've listened a bit to a channel called "fire in a bottle" on youtube. He has an interesting theory that being fat is essentially being in a torpid state. Basically a lot of animals need the ability to store fat for winter or dry seasons when food availability is low. Keep in mind that cortisol, serotonin, adrenaline etc aren't in themselves bad but when dysregulated becomes a problem. I also listened to an old episode of Dannys podcast with Georgi, where Georgi mentions that a persons specific ailment, no matter what it is, might just be that specific persons "weak point" and can be triggered by anything that hinders oxidative metabolism. I'm not bright enough to have a biochemical understanding, but my understanding is that being fat and the reason for it is probably varied between individuals.

 

[Bioenergy_Space]

being fat and the reason for it is probably varied between individuals.

Yes, individuals vary widely in their susceptibility to particular stressors. Sleep deprivation may make one person fat, and another will just have worse mood and not gain weight. But I do believe that there are generalities in the obesity/insulin resistance state.