PUFAs, cardiolipin, ATP production and obesity

Hans

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As we all know, PUFAs are a metabolic toxin. One of the mechanisms how a high fat diet promotes obesity and metabolic syndrome is by remodeling cardiolipin. Cardiolipin is a unique mitochondrial phospholipid that contains 4 fatty acids. Its main goal is to stabilize the complexes of the electron transport chain so that energy production can be optimized. Peat has mentioned that babies are born with their cardiolipin completely saturated (consisting of saturated fat). As they start to eat more PUFAs, their cardiolipin becomes more unsaturated (first linoleic acid, then more unsaturated fat such as arachidonic acid, EPA and DHA), which makes it prone to oxidation by free radicals. Also, PUFAs are fluid, which reduces the stability of the complexes of the ETC, thus reducing energy production. And this is exactly what this study found.

"Compared to the control diet, the high fat diet remodeled liver mitochondrial phospholipid acyl chain composition by 0.6-5.3-fold with notable increases in n-6 and n-3 polyunsaturation. The remodeling in the liver was accompanied by diminished complex I to III respiratory enzyme activity by 3.5-fold. Finally, qRT-PCR analyses demonstrated an upregulation of liver mRNA levels of tafazzin, which contributes to cardiolipin remodeling. Altogether, these results demonstrate that diet-induced obesity remodels acyl chains in the mitochondrial phospholipidome and exerts tissue specific impairments of respiratory enzyme activity." (R)

So all in all, even without being damaged by oxidative stress, both omega 6 and 3 can unsaturate cardiolipin and make the ETC less effective. Once the ETC becomes less effective, there will be more electron leak, which will damage the unsaturated cardiolipin and serious cell damage and possible cell death as well.
Depleting PUFA is one of the best ways to undo this. Feeding rats saturated fat restore cardiolipin back to normal and rescued defective energy metabolism.
 
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This study looked specifically at DHA.

"Moreover, DHA lowered enzyme activities of respiratory complexes I, IV, V, and I+III. Mechanistically, the reduction in enzymatic activities were not driven by a dramatic reduction in the abundance of supercomplexes. Instead, replacement of tetralinoleoyl-CL with tetradocosahexaenoyl-CL in biomimetic membranes prevented formation of phospholipid domains that regulate enzyme activity. Tetradocosahexaenoyl-CL inhibited domain organization due to favorable Gibbs free energy of phospholipid mixing. Furthermore, in vitro substitution of tetralinoleoyl-CL with tetradocosahexaenoyl-CL blocked complex-IV binding. Finally, reintroduction of linoleic acid, via fusion of phospholipid vesicles to mitochondria isolated from DHA-fed mice, rescued the major losses in the mitochondrial phospholipidome and complexes I, IV, and V activities. Altogether, our results show that replacing linoleic acid with DHA lowers select cardiac enzyme activities by potentially targeting domain organization and phospholipid-protein binding, which has implications for the ongoing debate about polyunsaturated fatty acids and cardiac health." (R)

They concluded that linoleic acid, an omega 6 with 2 double bonds, was actually better for the heart than and omega 3 with 6 double bonds. But they failed to realize that a less unsaturated fat was better than a highly unsaturated fat.
 

dabdabdab

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I remember reading about topical long chain saturated fats going straighly to the brain and becoming a part of its structure.
can that repair cardiolipin?
 
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Hans

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I remember reading about topical long chain saturated fats going straighly to the brain and becoming a part of its structure.
can that repair cardiolipin?
Studies using oral saturated fat have been shown to "repair" cardiolipin, so topical should also work since they are being absorbed.
 

dabdabdab

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Studies using oral saturated fat have been shown to "repair" cardiolipin, so topical should also work since they are being absorbed.
Can we conclude that eating saturated fat is better than no or low fat diet(in that regard) ?
Also do you think there could be any difference in topical vs oral administration?
cuz topical long chain sat fats got stored the same length they were.
but eating them, would result in shorter chain fatty acids after digestion.
 
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Hans

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Can we conclude that eating saturated fat is better than no or low fat diet(in that regard) ?
Also do you think there could be any difference in topical vs oral administration?
cuz topical long chain sat fats got stored the same length they were.
but eating them, would result in shorter chain fatty acids after digestion.
Your body can create its own saturated, monounsaturated and polyunsaturated fat (Mead acid for example) endogenously from carbs. But this only becomes significant after fat intake is greatly restricted.
Tissue concentrations of fat usually reflect dietary intake. If you consume more PUFA, more PUFA is being stored. Same thing for SFAs. Oral intake of SFA doesn't cause shortening unless they actually go through partial beta-oxidation or peroxisomal beta-oxidation. There is a study showing that topical application of SFA can promote elongation, so that's one thing to consider, however, the absorption of topical fat isn't that great.
 

dabdabdab

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Your body can create its own saturated, monounsaturated and polyunsaturated fat (Mead acid for example) endogenously from carbs. But this only becomes significant after fat intake is greatly restricted.
Tissue concentrations of fat usually reflect dietary intake. If you consume more PUFA, more PUFA is being stored. Same thing for SFAs. Oral intake of SFA doesn't cause shortening unless they actually go through partial beta-oxidation or peroxisomal beta-oxidation. There is a study showing that topical application of SFA can promote elongation, so that's one thing to consider, however, the absorption of topical fat isn't that great.
thanks for the answer
 

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