haidut

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Over the years I have posted a number of studies on the roles of PUFA metabolites such as prostaglandins and leukotrienes in many chronic conditions including cancer, Alzheimer, Parkinson, ALS, MS, CVD, etc. For those that are new to this issue, COX enzymes are responsible for prostaglandin synthesis while LOX enzymes are responsible for leukotriene synthesis. The source material (substrates) for COX/LOX are PUFA such as arachidonic acid, DHA/EPA, and even the arachidonic acid precursor linoleic acid. Now, the study below links one of the PUFA metabolizing enzymes - 12/15LOX (ALOX15) is crucial for the development of heart failure after acute ischemic heart attack.

ALOX15 - Wikipedia

When that enzyme was abrogated/inhibited, there was much better recovery from the heart attack and heart fibrosis (failure) did not develop. In addition, abrogation/inhibition of that enzyme also lowered levels of a highly selective and specific biomarker of diabetes - aminoadipic acid.

Alpha-aminoadipate pathway - Wikipedia

As such, the study suggests that PUFA is responsible (through its metabolites) for organ fibrosis/failure and diabetes, and inhibiting PUFA metabolism is therapeutic for both conditions. Since PUFA restriction is an approach that addresses events earlier in the metabolic cascade than ALOX15 inhbition, IMO it is fair to say that avoiding dietary PUFA is therapeutic for both diabetes and heart failure.

https://www.metabolismjournal.com/article/S0026-0495(19)30077-0/fulltext

"...In mice, deletion of leukocyte responsive 12/15LOX enzyme altered homeostatic equilibria and lowered levels of diabetes biomarker α-aminoadipic acid with profound infarcted heart lipidomic remodeling in the acute HF, thereby delayed chronic HF. Deficiency of 12/15LOX in mice promoted cardiac healing and survival with: 1) marked decreased of 2-aminoadipic acid metabolite in plasma; 2) increased bioactive mediators cypoxins in the infarcted heart in compensation with LOX-derived SPMs; and 3) profound changes in leukocytes trafficking and metabolites signaling of hexoses, amino acids, biogenic amines, acylcarnitines, glycerophospholipids, and sphingolipids in acute HF with obvious structural and fibrotic remodeling in chronic HF syndrome."

News - How the enzyme lipoxygenase drives heart failure after heart attacks

"...Heart failure after a heart attack is a global epidemic leading to chronic heart failure pathology. About 6 million people in the United States and 23 million worldwide suffer from this end-stage disease that involves dysfunction of the heart, a change that clinicians call cardiac remodeling. Despite medical advances, 2 to 17 percent of patients die within one year after a heart attack due to failure to resolve inflammation. More than 50 percent die within five years."

How the enzyme lipoxygenase drives heart failure after heart attacks: Heart failure after a heart attack is a global epidemic, with 50 percent of patients dying within five years

"...This work follows his 2017 discovery that knocking out 12/15 lipoxygenase, or 12/15LOX, a lipid-modifying enzyme that competes with two other lipid-modifying enzymes, leads to increased survival in a mouse model of heart failure after a heart attack. In a study now published online ahead of print in the journal Metabolism: Clinical and Experimental, Halade and colleagues detail the profound lipidomic and metabolic signatures and the modified leukocyte profiling that delay heart failure progression and provide improved survival in 12/15LOX-deficient mice. Only 6 percent of the 12/15LOX-deficient mice died in the progression of chronic heart failure, 56 days after heart attack, while 38 percent of mice with normal 12/15LOX had mortality due to heart failure or rupture. Specifically, the researchers quantified changes in the metabolome, lipidome and immune profiles during acute heart failure, one day after heart attack, and during chronic heart failure, eight weeks after heart attack. They found that the 12/15LOX-deficient mice biosynthesized the signaling molecules epoxyeicosatrienoic acids -- also known as EETs or cypoxins -- in left ventricle heart tissue after heart attack to facilitate cardiac healing. The lipoxygenase-deficient mice also had reduced amounts of the diabetes risk biomarker 2-aminoadipic acid and had profound alterations of plasma metabolic signaling of hexoses, amino acids, biogenic amines, acylcarnitines, glycerophospholipids and sphingolipids during acute heart failure. These changes are accompanied by delayed heart failure and improved survival. "Future studies are warranted to define the molecular network of the lipidome and metabolome in acute and chronic heart failure patients," Halade said, though he notes this needs to be preceded by work with other animal models. "Collectively, our studies have discovered a novel link of LOX signaling between lipidomic and metabolic signatures in acute and chronic heart failure syndrome."
 

LucH

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Thanks for bringing this link / Info.
I Knew EPA acted on 5-Lox (inflammation) and on 12-Lox but wasn't conscious of other impact, other than "depressed pathway" for toxins (delayed). Thanks.
NB: Ok, short sighted ...
Here have I got some details about functions of those prostaglandines:
The LOX products are responsible for human inflammatory responses ( 2 ), and they are also implicated in a variety of human diseases. 5-LOX is involved in asthma ( 3 ) and cancer ( 4, 5 ). 12-LOX is involved in psoriasis ( 6 ), hypertension ( 7, 8 ), hemostasis ( 9–12 ), diabetes ( 13, 14 ), and cancer ( 5, 15, 16 ), and 15-LOX is involved in atherosclerosis ( 17 ) and cancer ( 5, 18 ).
Source: http://www.jlr.org/content/53/12/2546.full.pdf
5-Lox: inflammation
12-Lox: regulation of human platelet function ( important regulatory role)
 

haidut

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Thanks for bringing this link / Info.
I Knew EPA acted on 5-Lox (inflammation) and on 12-Lox but wasn't conscious of other impact, other than "depressed pathway" for toxins (delayed). Thanks.
NB: Ok, short sighted ...
Here have I got some details about functions of those prostaglandines:
The LOX products are responsible for human inflammatory responses ( 2 ), and they are also implicated in a variety of human diseases. 5-LOX is involved in asthma ( 3 ) and cancer ( 4, 5 ). 12-LOX is involved in psoriasis ( 6 ), hypertension ( 7, 8 ), hemostasis ( 9–12 ), diabetes ( 13, 14 ), and cancer ( 5, 15, 16 ), and 15-LOX is involved in atherosclerosis ( 17 ) and cancer ( 5, 18 ).
Source: http://www.jlr.org/content/53/12/2546.full.pdf
5-Lox: inflammation
12-Lox: regulation of human platelet function ( important regulatory role)

Thanks. Btw, tocopherols inhibit both COX and LOX and this is probably one of the main mechanisms through they protect against heart and brain disease. Aspirin is believed to be COX inhibitor only but some of the latest studies show it can target LOX as well.
 

BigChad

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Thanks. Btw, tocopherols inhibit both COX and LOX and this is probably one of the main mechanisms through they protect against heart and brain disease. Aspirin is believed to be COX inhibitor only but some of the latest studies show it can target LOX as well.

Do tocotrienols have any anti prostaglandin or other beneficial effects? Ive heard they "improve liver function" among other things, not sure how they do so
 

cedric

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Jul 26, 2018
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PUFA's react with iodine
Iodine value - Wikipedia

Isn't iodine a protective factor against PUFA oxidation? Maybe PUFA toxicity is the sign of iodine deficiency?
People of Okinawa, Creta, Sardinia -they eat a lot fish, seafood , rich in PUFA and they live over 100 years.
Dr. M.Sircus (?) wrote that iodine is able to mobilize trans-fats from arterial plaque making them soluble.
Iodine is a primal antioxidant
https://pdfs.semanticscholar.org/9496/5003f5520c1593bc5db3c2a7e8ee7bdd0df7.pdf

https://pdfs.semanticscholar.org/d4e4/3bb1b17362aae6bdf11fa2f70457d43c0932.pdf

Evolutionary roots of iodine and thyroid hormones in cell–cell signaling

SAGE Journals: Your gateway to world-class research journals

AFH LIBRARY - Iodine: Bring Back the Universal Nutrient in Medicine.

AFH LIBRARY - Iodine and Chelation

AFH LIBRARY - Transdermal Iodine.

Evolutionary roots of iodine and thyroid hormones in cell–cell signaling
Evolutionary roots of iodine and thyroid hormones in cell–cell signaling
Published:

23 June 2009
 
Last edited:
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