Why glucose oxidation is preferable to fatty acid oxidation

haidut

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I have seen this question come up many times on the forum. This study offers a potential answer and even though it focuses only on brain metabolism the given reasons are applicable for most other tissues as well.

http://www.ncbi.nlm.nih.gov/pubmed/23921897

"...It is puzzling that hydrogen-rich fatty acids are used only poorly as fuel in the brain. The long-standing belief that a slow passage of fatty acids across the blood-brain barrier might be the reason. However, this has been corrected by experimental results. Otherwise, accumulated nonesterified fatty acids or their activated derivatives could exert detrimental activities on mitochondria, which might trigger the mitochondrial route of apoptosis. Here, we draw attention to three particular problems: (1) ATP generation linked to β-oxidation of fatty acids demands more oxygen than glucose, thereby enhancing the risk for neurons to become hypoxic; (2) β-oxidation of fatty acids generates superoxide, which, taken together with the poor anti-oxidative defense in neurons, causes severe oxidative stress; (3) the rate of ATP generation based on adipose tissue-derived fatty acids is slower than that using blood glucose as fuel. Thus, in periods of extended continuous and rapid neuronal firing, fatty acid oxidation cannot guarantee rapid ATP generation in neurons. We conjecture that the disadvantages connected with using fatty acids as fuel have created evolutionary pressure on lowering the expression of the β-oxidation enzyme equipment in brain mitochondria to avoid extensive fatty acid oxidation and to favor glucose oxidation in brain."
 

brandonk

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haidut said:
I have seen this question come up many times on the forum. This study offers a potential answer and even though it focuses only on brain metabolism the given reasons are applicable for most other tissues as well.
Fatty acid oxidation is preferable in some tissues, especially if you are oxidizing ketones. Arguably, the most immediate improvement to metabolic state that can be made is the oxidation of certain kinds of fatty acids, perhaps by brown or beige adipose tissue.

I know how well-meaning and well-read you are, and I guess I fear that by making overly general statements, at least in the title of the thread, you may be more (not less) vulnerable to the attacks you worry about (i.e., that Ray Peat is called a "wacko" by others as you've said).
 

Suikerbuik

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brandonk said:
post 118596 Arguably, the most immediate improvement to metabolic state that can be made is the oxidation of certain kinds of fatty acids, perhaps by brown or beige adipose tissue.

Why brown or beige adipose tissue?
 
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brandonk

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Suikerbuik said:
brandonk said:
post 118596 Arguably, the most immediate improvement to metabolic state that can be made is the oxidation of certain kinds of fatty acids, perhaps by brown or beige adipose tissue.

Why brown or beige adipose tissue?
This tissue has been observed to suddenly appear on PET scans, when it is somehow activated, as dark (hence the name brown or beige) patches of adipose tissue, typically around the the neck and collar bone, but also in smaller striations in muscles everywhere.

Once activated, the theory would go that mitochondria come alive, lending the dark color, and oxidize fatty acids through largely uncoupled respiration, generating large quantities of heat and carbon dioxide, and in theory boosting the redox state of the organism. BMR has been claimed to increase by 200-300 calories.

A related theory is that activating this oxidation of fatty acids may drain or pull free fatty acids out of the blood, as an additional benefit.

Some studies have claimed the brown or beige adipose tissue can be activated by prolonged, mild hypercapnia or hypoxia, by ingested ketones or by prolonged exposure to cold.
 
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Sheila

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I knew a gentleman who had a pronounced Cushing's hump of fat tissue ("buffalo hump") on the back of his neck and certainly ran in cortisol most of the time. I wondered at the time if the fat deposition (which he had removed and of course it grew back) was some adaptive change - and especially why did placement occur there? To feed the brain easier? That's probably a long shot but the best I could come up with. But on further research, and why it might be interesting on this thread, is that such fat deposits in this 'disease' are brown. Production of brown fat is also a known effect of exogenous cortisone therapy (Aronson et al. 1954). So the sudden appearance on CT might be down to acute stress or cortisol??? This gentleman would be a hyperventilating, high blood pressure, round tummy (but thinner limbs, moon face), thinning skin, balding headed, over-working, low carber but prolonged exposure to cold, no, not here! Any thoughts?
Thank you, Sheila.
 

brandonk

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I do see this, which suggests that the Cushing's hump is a metabolic disorder that at least originates in brown fat, even if the hump becomes unrecognizable once it is overgrown:

http://www.ncbi.nlm.nih.gov/pubmed/2381166

Also, brown fat is known as the "hibernating fat" because it seems to warm the animal when it awakens from torpor or hibernation, so one would expect that it would respond to the cortisol surge that awakens the animal from torpor with a kind of stress response.

https://books.google.com/books?id=e5qjA ... &q&f=false

But for more Peaty purposes, the brown fat also responds to things that are not stressful, such as slow breathing and ingested ketones (and even mild cold temperatures).
 

Suikerbuik

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brandonk said:
Suikerbuik said:
brandonk said:
post 118596 Arguably, the most immediate improvement to metabolic state that can be made is the oxidation of certain kinds of fatty acids, perhaps by brown or beige adipose tissue.

Why brown or beige adipose tissue?
This tissue has been observed to suddenly appear on PET scans, when it is somehow activated, as dark (hence the name brown or beige) patches of adipose tissue, typically around the the neck and collar bone, but also in smaller striations in muscles everywhere.

Once activated, the theory would go that mitochondria come alive, lending the dark color, and oxidize fatty acids through largely uncoupled respiration, generating large quantities of heat and carbon dioxide, and in theory boosting the redox state of the organism. BMR has been claimed to increase by 200-300 calories.

A related theory is that activating this oxidation of fatty acids may drain or pull free fatty acids out of the blood, as an additional benefit.

Some studies have claimed the brown or beige adipose tissue can be activated by prolonged, mild hypercapnia or hypoxia, by ingested ketones or by prolonged exposure to cold.

Okay thanks. I have not seen theories on BAT 'draining' FFAs, but it makes sense as this happens with glucose as well.
I know of PPARa/g stimulating BAT, and increased CO2 via PGC1a, but I was not aware of ketones. Do you have a study on hand? Or how else can this be done? I am not willing to try clenbuterol or prolonged cold exposure.
 
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brandonk

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Suikerbuik said:
post 118652
brandonk said:
Suikerbuik said:
brandonk said:
post 118596 Arguably, the most immediate improvement to metabolic state that can be made is the oxidation of certain kinds of fatty acids, perhaps by brown or beige adipose tissue.

Why brown or beige adipose tissue?
This tissue has been observed to suddenly appear on PET scans, when it is somehow activated, as dark (hence the name brown or beige) patches of adipose tissue, typically around the the neck and collar bone, but also in smaller striations in muscles everywhere.

Once activated, the theory would go that mitochondria come alive, lending the dark color, and oxidize fatty acids through largely uncoupled respiration, generating large quantities of heat and carbon dioxide, and in theory boosting the redox state of the organism. BMR has been claimed to increase by 200-300 calories.

A related theory is that activating this oxidation of fatty acids may drain or pull free fatty acids out of the blood, as an additional benefit.

Some studies have claimed the brown or beige adipose tissue can be activated by prolonged, mild hypercapnia or hypoxia, by ingested ketones or by prolonged exposure to cold.

Okay thanks. I have not seen theories on BAT 'draining' FFAs, but it makes sense as this happens with glucose as well.
I know of PPARa/g stimulating BAT, and increased CO2 via PGC1a, but I was not aware of ketones. Do you have a study on hand? Or how else can this be done? I am not willing to try clenbuterol or prolonged cold exposure.
Veech has been a longtime proponent of ketones since his early work in the 70s with Cahill. Ketone esters and salts are other ways of ingesting dietary ketones, along with coconut oil or its medium chain fractions.

Re the glucose response you mention, Veech has pointed out that ketones act like insulin and raise glucose within the cell - this is not via GLUT4 - lower glucose in the circulation would call forth less insulin from the pancreas and cause less need for insulin. It seems to be similar to progesterone and even potassium in this way.

http://www.ncbi.nlm.nih.gov/pubmed/23909803
http://www.jlr.org/content/early/2014/0 ... 9.full.pdf
http://www.nyas.org/MediaPlayer.aspx?mi ... 70771d2955
http://www.fasebj.org/content/early/201 ... 0.full.pdf
 
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brandonk

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jyb said:
A related post on ATP/CO2 with different fuel sources.
This blogger acknowledges that there is less CO2 produced when oxidizing saturated fat, but to him, that's a good thing, because it means you can breathe less often (sort of good if you are a diver for pearls, I guess).

Veech's (and Peat's) point about ketones producing far more ATP (and with uncoupled respiration far more CO2) is really a very different point.* Veech describes the ATP equations here:
http://www.coconutketones.com/pdfs/veec ... ations.pdf

*As the blogger says: "Ketones are not as arithmetically simple as fatty acids but we all know, from Veech and D'Agostino's work, that magical indeed they are."
 

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