Anders86

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Uridine is already formed in humans from breakdown of oral CDP-choline. You only need extra uridine (oral - not sublingual - with food and carbs) if you take Alpha-GPC, egg yolks, choline bitartrate or choline citrate and you don't consume milk (source of orotate - uridine precursor) or you have the genetic flaw that prevents uridine production through the orotate pathway (unlikely you have this).

Too much, too high uridine too long can probably cause harm - extremely underresearched substance - so am cautious about it. High blood uridine mimics fasting conditions, although so far (2016) this is basically just correlation.

Traditionally Kennedy pathway - in liver, anyway - is limited by CTP:phosphocholine cytidylyltransferase which is limited by endogenous orotate/Uridine/UMP production, but in other circumstances other variables enter such as DAG abundance.

The main point of my posts was just to point out that PEMT is probably responsible for export of polyunsaturated phospholipids from the liver, while the less stress-related Kennedy pathway should tend to produce Ray Peat approved phospholipids. There is a whole other dimension when it comes to tissue- and organ-specific phospholipid synthesis outside liver.

You probably know of the Mr.Happy stack? Seems like most got mixed results. But I wouldnt be surprised if Mr.Happy is still going strong.
 

Amazoniac

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In theory that product is the best thing available if you space it out. Except I don't know how much gets wasted and how much actually gets where it needs to be (including liver) pre-formed. Otherwise you might as well get choline, spread-out. I would probably take a little uridine anyway for any of it that breaks down.
I was wondering about this as vvcll. These might interest you:
- Intestinal absorption of polyenephosphatidylcholine in man
- Intracellular digestion of saturated and unsaturated phospholipid liposomes by mucosal cells. Possible mechanism of transport of liposomally entrapped macromolecules across the isolated vascularly perfused rabbit ileum - ScienceDirect

@haidut mentioned that what's expensive is the palmitic acid part. Depending on how much isn't absorbed intact, it could be better to sell only the stearic acid form, lowering the price (simplifying the process alone must lower it) and making it feasible as a choline supplement without sacrificing its purpose. Many of the studies linked on the Mitolipin thread are for phosphatidylcholine without being specific anyway.

Perhaps a meal that provides enough palmitic acid when consuming the supplement might encourage its incorporation during reassemblage.
 

Terma

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You probably know of the Mr.Happy stack? Seems like most got mixed results. But I wouldnt be surprised if Mr.Happy is still going strong.

Yeah, tried it years ago with very temporary brain improvement and petered out quickly.

I think that my observations probably have no relation to the subjective effects reported by that stack. The phospholipid composition issue I talk about (w.r.t. fructose) is more long-term and outside the brain.

Furthermore, I think in retrospect it's a very careless protocol, because blood levels of uridine have not been interpreted by anyone other than some rodent scientists in 2016 (was posted here somewhere) which was not suggestive of anything you'd want.

I did get significant benefit from consuming sardines in the past, but apart from omega-3 they contain very high phosphatidylserine and other nutrients. I never achieved any progress using omega-3 capsules.

The NGF angle is probably better, although (like BDNF) it tends to occur through hormesis and it's hard to determine if the hormesis part is necessary or not.
 

Terma

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I was wondering about this as vvcll. These might interest you:
- Intestinal absorption of polyenephosphatidylcholine in man
- Intracellular digestion of saturated and unsaturated phospholipid liposomes by mucosal cells. Possible mechanism of transport of liposomally entrapped macromolecules across the isolated vascularly perfused rabbit ileum - ScienceDirect

@haidut mentioned that what's expensive is the palmitic acid part. Depending on how much isn't absorbed intact, it could be better to sell only the stearic acid form, lowering the price (simplifying the process alone must lower it) and making it feasible as a choline supplement without sacrificing its purpose. Many of the studies linked on the Mitolipin thread are for phosphatidylcholine without being specific anyway.

Perhaps a meal that provides enough palmitic acid when consuming the supplement might encourage its incorporation during reassemblage.

Oh yes. The first one you linked I'm very familiar with (and in humans, not rats! albeit approximate at best). It says that most of the ingested phospholipids get half-hydrolyzed in the intestine, so only one of the two lipid tails gets absorbed intact, while the proportion of fully intact absorbed phospholipids is rather low (20% or less at best, and that figure being from rat studies).

I give some leeway to haidut & co. because these experiments were all done using common phospholipids from soy and such, so it's not 100% certain what happens to fully saturated phospholipids when ingested (two palmitic acids or two stearic acids) since no one cares, but given the available evidence I assume they're not absorbed intact and it's better to get the liver to produce the desired phospholipids for you instead (not to mention, much cheaper, assuming it works).

Your second link I'll have to read later, thanks.
 

ddjd

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Uridine is already formed in humans from breakdown of oral CDP-choline. You only need extra uridine (oral - not sublingual - with food and carbs) if you take Alpha-GPC, egg yolks, choline bitartrate or choline citrate and you don't consume milk (source of orotate - uridine precursor) or you have the genetic flaw that prevents uridine production through the orotate pathway (unlikely you have this).

Too much, too high uridine too long can probably cause harm - extremely underresearched substance - so am cautious about it. High blood uridine mimics fasting conditions, although so far (2016) this is basically just correlation.

Traditionally Kennedy pathway - in liver, anyway - is limited by CTP:phosphocholine cytidylyltransferase which is limited by endogenous orotate/Uridine/UMP production, but in other circumstances other variables enter such as DAG abundance.

The main point of my posts was just to point out that PEMT is probably responsible for export of polyunsaturated phospholipids from the liver, while the less stress-related Kennedy pathway should tend to produce Ray Peat approved phospholipids. There is a whole other dimension when it comes to tissue- and organ-specific phospholipid synthesis outside liver.
in this longecity thread they discuss the same uridine + dha + choline stack. But they suggest Folate and b12 is essential when supplementing Uridine

GPC (choline), Uridine, DHA - Brain Health - LONGECITY
 

Amazoniac

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Oh yes. The first one you linked I'm very familiar with (and in humans, not rats! albeit approximate at best). It says that most of the ingested phospholipids get half-hydrolyzed in the intestine, so only one of the two lipid tails gets absorbed intact, while the proportion of fully intact absorbed phospholipids is rather low (20% or less at best, and that figure being from rat studies).

I give some leeway to haidut & co. because these experiments were all done using common phospholipids from soy and such, so it's not 100% certain what happens to fully saturated phospholipids when ingested (two palmitic acids or two stearic acids) since no one cares, but given the available evidence I assume they're not absorbed intact and it's better to get the liver to produce the desired phospholipids for you instead (not to mention, much cheaper, assuming it works).

Your second link I'll have to read later, thanks.
There are some positive reviews there that I suppose were from people taking the suggested serving, which is too low to be providing enough choline to make a difference; so any effect must've been due to what's intended to do. However! It used to have D and M and S and O and various members were probably applying it on their skin. It no longer has it and perhaps when ingested it's more likely to be cleaved.

Saturazione mentioned that the tocopherols can be confounding factors as well.

--
The use of natural and synthetic phospholipids as pharmaceutical excipients
 
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Hans

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If both PC and PE can be made through the Kennedy pathway from saturated DAG, won't that make synthesized PC through PEMT be less of a problem, because it wouldn't be as unsaturated and prone to oxidation?
 

Terma

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If both PC and PE can be made through the Kennedy pathway from saturated DAG, won't that make synthesized PC through PEMT be less of a problem, because it wouldn't be as unsaturated and prone to oxidation?
I'm not sure why (definitely something to research in more detail), but ethanolamine always seems to associate with unsaturated fatty acids [in other words I'd be surprised if much saturated PE would get produced that way]. I don't know if it's the molecule itself, a cellular localization of the production thing (i.e. from the different organelles), or something else, but in the studies I linked above it's noted a few times PEMT in liver ends up producing more unsaturated species.

Although this obviously isn't the liver, you can find the clearest association in post-mortem human brain slice studies, phosphatidylethanolamine is the most unsaturated (o-6) phospholipid, striking difference: https://pdfs.semanticscholar.org/edad/e0ebfe50de08eb95886a0505a2b42c108d9f.pdf

Sorry I'm too screwed up to make a thorough post this weekend (like that's even my style).
 
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Terma

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^ That's interesting about saturation lowering Na,K-ATPase, I leave someone else to interpret that in context of this forum...

------------------

Follow-up to what I posted (kind of off-topic but oh well - it suggests there could be an equivalent in skeletal muscle), this may be in mice but gives some potentially very important support for the fructose+choline+uridine liver-targeting combo:

[Some caution due to fact it's mice]

Identification of a Physiologically Relevant Endogenous Ligand for PPARα in Liver

Abstract
PPARα is activated by drugs to treat human disorders of lipid metabolism. Its endogenous ligand is unknown. PPARα-dependent gene expression is impaired with inactivation of fatty acid synthase (FAS), suggesting that FAS is involved in generation of a PPARα ligand. Here we demonstrate the FAS-dependent presence of a phospholipid bound to PPARα isolated from mouse liver. Binding was increased under conditions that induce FAS activity and displaced by systemic injection of a PPARα agonist. Mass spectrometry identified the species as 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Knockdown of CEPT1, required for phosphatidylcholine synthesis, suppressed PPARα-dependent gene expression. Interaction of 16:0/18:1-GPC with the PPARα ligand binding domain and co-activator peptide motifs was comparable to PPARα agonists, but interactions with PPARδ were weak and none were detected with PPARγ. Portal vein infusion of 16:0/18:1-GPC induced PPARα-dependent gene expression and decreased hepatic steatosis. These data suggest that 16:0/18:1-GPC is a physiologically relevant endogenous PPARα ligand.

PPARα upregulates fatty acid oxidation in the liver to help lower FFA and other problems, and ligand appears to be the phosphatidylcholine 16:0/18:1-GPC. PPARα is a major sought target for diseases. In other words it also fixes fructose overloads.

Here we demonstrate PPARα binding of a discrete phospholipid, 16:0/18:1-GPC, in mammalian liver in the presence of FAS, when PPARα is active, but not in the absence of FAS, when PPARα is not.

Our current results show that the phosphatidylcholine molecular species 16:0/18:1-GPC binds PPARα at an activating ligand binding site (reflected by its displacement with a synthetic PPARα ligand in vivo) when FAS enzyme activity is present. 16:0/18:1-GPC is the only FAS-dependent phosphatidylcholine species we identified bound to PPARα in vivo. However, two other phosphatidylcholine species, 16:0/18:2-GPC and 18:1/18:1-GPC, were also co-purified with tagged PPARα from liver and their interactions with the PPARα ligand binding domain in vitro (Supplemental Figure 5) were indistinguishable from those of 16:0/18:1-GPC. The failure to discriminate between these three GPCs in vitro may be due to differential interactions between ligands and ligand binding domains in vitro as opposed to ligands and full length receptors in vivo. 16:0/18:2-GPC and 18:1/18:1-GPC, but not 16:0/18:1-GPC, remained bound to PPARα in the absence of hepatic FAS, a condition characterized by a striking decrease in PPARα-dependent gene expression. Their association with the receptor in the absence of appropriate activation of gene expression suggests that the binding of 16:0/18:2-GPC and 18:1/18:1-GPC is not sufficient for receptor activation, but we cannot exclude the possibility that the presence of these additional species may be necessary for receptor activation.

One interpretation of our findings is that FAS, which synthesizes predominantly the saturated fatty acid palmitate (16:0), preferentially channels newly synthesized palmitate through diacylglycerol to the site of phosphatidylcholine synthesis for generation of the PPARα ligand.

This is what I wrote earlier in the thread.

Fructose + (choline + uridine) = 16:0/18:1-GPC.

In cultured cells, SREBPs stimulate the synthesis of phosphatidylcholine (but not other phospholipids), and this effect is attenuated by the FAS-inhibitor cerulenin (Ridgway and Lagace, 2003). Figure 7F shows how fatty acid synthesis, phosphatidylcholine synthesis, and PPARα signaling appear to be related based on the current findings.

Interesting remark: According to another study, SREBP stimulates synthesis of only phosphatidylcholine, not serine/inositol/ethanolamine.

Implied, there must be an intact PI3K/Akt/mTorC1->SREBP pathway (and of course FAS) for the PC synthesis to work. So it could get compromised in extremely insulin-insensitive livers. (Wikipedia Sterol regulatory element-binding protein - Wikipedia notes that "mTORC1 activation is not sufficient to stimulate hepatic SREBP-1c in the absence of Akt signaling", so Akt signaling is important, suggesting influence by insulin though other things can compensate partially, e.g. alpha-lipoic acid)

The binding of 16:0/18:1-GPC to PPARα was decreased in the absence of FAS and significantly increased under conditions (high carbohydrate feeding) that induce FAS activity

(The insulin remark, bastardized)

Our results showing that portal vein infusion results in nuclear before cytoplasmic accumulation (Supplemental Fig. 7) are consistent with an uncharacterized conduit for phospholipids to the nucleus. Since the portal vein drains the intestine, the anatomic origin of nutrients, the results also suggest that providing a GPC ligand in the diet, if it were able to access the portal vein at sufficient concentrations, could activate hepatic PPARα. The method of infusion, utilizing the portal vein, is likely important.
This indirectly supports the observation that you cannot take GPC orally because it is only a choline prodrug across the gut barrier; they injected directly into protal vein.

They injected the full 16:0/18:1-GPC molecule, not just GPC. Is not clear how much intact 16:0/18:1-GPC makes it to the cellular target. So I'm unsure about the absolute necessity of the FAS enzyme at least "existing" for the temporal promotion of PPARα, regardless of its products.

The safe way to interpret is to promote fructose, because it makes sense in all the cases, provided phosphatidylcholine is sufficiently supported.

Note: Of course in rodents super high-dose fructose actually worsens PPARα (Reversal of High dietary fructose-induced PPARα suppression by oral administration of lipoxygenase/cyclooxygenase inhibitors), so it must properly supported.

Phosphatidylcholine is ubiquitous in the cell and comprises a substantial proportion of the nuclear volume. It would have a limited capacity to regulate PPARα if high nuclear concentrations ensured constant occupation of the ligand binding site, but the putative PPARα ligand we identified, 16:0/18:1-GPC, is a minor PtdCho species in liver as shown by the current work (Results) and previous work (Hsu et al., 1998), consistent with a signaling role for this molecule. Conversely, 16:0/18:1- GPC is the most abundant PtdCho in brain (Hsu et al., 1998), raising the possibility that a different PtdCho species may activate PPARα in this tissue.

This research applies only to the liver for now. 16:0/18:1-GPC usually is not present in liver in major amounts, so it amounts to be a distinct signaling molecule for PPARα. It may have special meaning to the liver (and possibly to the liver only), or it's related to saturation.

----------------------------

Extra info from Results and Supplement 1:


Curiously, these fatty acids (so abundant that they cause fatty liver) from the periphery (that we have referred to as “old ” fat as opposed to “new” fat from de novo lipogenesis or diet) are unable to activate PPARα, suggesting (based on the current work) that they are unavailable for GPC synthesis. Lipids from the periphery enter the liver via the hepatic artery while those from the diet enter via the portal vein. The hepatic artery and portal vein comprise anatomically distinct regions of the portal triad, and it is possible that hepatocytes in those different segments respond differently to lipid signals.

Curiously, they suggest that fatty acids arriving from the portal vein only can activate PPARα, not circulating FFAs, due to a separation in liver anatomy. Don't know if mouse-specific effect - something to read about.

Rapid displacement of 16:0/18:1-GPC by the synthetic ligand Wy14,643 might reflect a relatively lower affinity of 16:0/18:1-GPC for PPARα as compared to other receptor-associated species that were not displaced, such as 16:0/18:2-GPC (m/z 764) and 18:1/18:1-GPC (m/z 793).

There is some potential for other phosphatidylcholine species (unsaturated) "crowding out" PPARα, as they bind to it without activating it.

Endogenous synthesis involves the successive action of choline kinase (CK) and CTP:phosphocholine cytidylyltransferase (CCT) to yield CDP-choline (Kent, 2005). This substrate reacts with diacyglycerol (DAG) to yield phosphatidylcholine (PtdCho) through the action of one of two enzymes, choline phosphotransferase 1 (ChPT1), found in the Golgi, and choline-ethanolamine phosphotransferase-1 (CEPT1), found in the nucleus as well as the ER (Henneberry et al., 2002). siRNA-mediated knockdown of these enzymes was achieved in cultured mouse hepatoma cells (Figure 6B), followed by assessment of PPARα-dependent genes. Inactivation of ChPT1, the Golgi enzyme, had no effect on ACO or CPT-1 (Figure 6C). However, knockdown of CEPT1, the nuclear/ER enzyme, decreased PPARα-dependent genes, an effect that was rescued by exogenous 16:0/18:1-GPC (Figure 6D), consistent with the notion that endogenous 16:0/18:1-GPC activates PPARα and that FAS-dependent 16:0/18:1-GPC is an endogenous PPARα ligand.

In this pathway, it must have been choline-ethanolamine phosphotransferase-1 (CEPT1), not choline phosphotransferase 1 (ChPT1).

Here the authors only suggest the Kennedy pathway, but CEPT1 knockdown also affects phosphatidylethanolamine synthesis, so I can't see anything that excludes a contribution from PEMT/methylation for the moment (I think evolutionarily that would be a handicap), except the general remark that PEMT seems to produce mostly unsaturated species.

We therefore extrapolated the doses in mice taking into account the direct intraportal
route, and tested doses ranging from 0.1 mg/day to 10 mg/day based on a 25 g mouse. We found
that rapid infusion (< 1 min) was optimal and that the lowest dose causing increased expression
of the PPARα target gene acyl-CoA oxidase was 10 mg/kg. Larger doses and slower infusion
rates resulted not only in poor solubility but also death due to portal vein thrombosis.

Gives mouse dose of minimum injected 16:0/18:1-GPC required in portal vein to enhance PPARα.

----------------------------

Site note: In other studies (I'm tired of linking and quoting at this point) PPARα among others regulates the expression of OCTN2, the Carnitine transporter for the outer cell membrane. Choline has also been suggested to increase OCTN2, although I don't think they were liver cells. I wonder if maybe choline does this by contributing to PPARα activation... needs a study.
 

Broken man

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Oh yes. The first one you linked I'm very familiar with (and in humans, not rats! albeit approximate at best). It says that most of the ingested phospholipids get half-hydrolyzed in the intestine, so only one of the two lipid tails gets absorbed intact, while the proportion of fully intact absorbed phospholipids is rather low (20% or less at best, and that figure being from rat studies).

I give some leeway to haidut & co. because these experiments were all done using common phospholipids from soy and such, so it's not 100% certain what happens to fully saturated phospholipids when ingested (two palmitic acids or two stearic acids) since no one cares, but given the available evidence I assume they're not absorbed intact and it's better to get the liver to produce the desired phospholipids for you instead (not to mention, much cheaper, assuming it works).

Your second link I'll have to read later, thanks.
I would like to ask, do you have any idea how can I make my liver to produce stearic acid phospholipid? Thank you.
 

Terma

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I would like to ask, do you have any idea how can I make my liver to produce stearic acid phospholipid? Thank you.

Indirectly... SCD1 desaturates C18:0 to C18:1 (Stearoyl-CoA Desaturase-1: Is It the Link between Sulfur Amino Acids and Lipid Metabolism?). In theory you simply kill liver SCD1 while still supporting fatty acid synthase, C16:0->C18:0 (elongase) and phospholipid synthesis. The stuff I mention in this thread is more likely to support oleic acid synthesis than stearic, though there's no way to quantify this (it's a mix of pro- vs anti-SCD1 factors: fructose+choline vs methionine restriction).

In a natural setting low SCD1 enzyme most likely means either protein and/or carb restriction (and maybe insulin resistance (Stearoyl-CoA Desaturase-1 Is Associated with Insulin Resistance in Morbidly Obese Subjects) - though I think this does not necessarily prevent SCD1 activation). You probably don't want to kill it off systemically or entirely, e.g. a pharmacological SCD1 inhibitor that makes it past the liver is a super bad idea (Loss of Stearoyl-CoA Desaturase-1 Improves Insulin Sensitivity in Lean Mice but Worsens Diabetes in Leptin-Deficient Obese Mice). I'm not sure there are safe options other than carb and/or amino acid restriction (and even then I would cycle the amino acid restriction).

Surprisingly, lowering SCD1 may actually be a valid method of promoting Kennedy, due to a compensatory mechanism:
Stearoyl-CoA Desaturase 1 Deficiency Increases CTP:Choline Cytidylyltransferase Translocation into the Membrane and Enhances Phosphatidylcholine Synthesis in Liver (**)
Those effects mirror the expected effects of methionine restriction on the phospholipid synthesis pathways. Note that PEMT lowers in this case, which is good but means that PE relatively increases.
Note that this (together with involvement of serine) is an argument against super-dosing fructose beyond what's required to promote DAG synthesis.
This situation becomes complicated by the lowered oleic acid content:
Our study has shown that SCD1 deficiency leads to decreased content of monounsaturated FA and increased content of polyunsaturated FA (mainly 20:4) in liver PLs, whereas the relative amount of saturated FA in hepatic PLs was not significantly altered due to Scd1 mutation (Table I).
This is, of course, of dubious desirability. You could maybe simply eat more oleic acid, though I'm not sure to what extent the exogenous oleic substitutes for the de novo synthesized oleic (cellular localization, etc.)

This takes another turn in the brain, because stearic acid - along with PUFA - is mainly found in the phospholipids PS and PE, rather than PC (***) (Fatty acid composition of human brain phospholipids during normal development. - PubMed - NCBI http://theses.gla.ac.uk/981/1/1998jamiesonphd.pdf). PS is especially dominated by C18:0, but PE is more abundant. So it suggests that incorporation of stearic acid is more likely with higher PS-PE:PC ratio (a scenario usually supported by dietary restriction), which is the opposite of this thread and what the previous study (**) suggests, which might represent temporal and combined factors.

I suppose you could increase linolenic acid intake (the safest form of omega-3) and it might lower SCD1 and help along PC followed by PS synthesis (though the PS might also derive from the PE). I wouldn't be surprised if ALA (alpha linolenic acid) supplements were actually a benefit by promoting a higher PC+PS:PE ratio. Here, PS is probably a "healthier" target than PE because PS is higher C18:0 and slightly lower PUFA, and furthermore is the phospholipid that contains most of the omega-3 (to counteract omega-6 effects) and because it's known to be able to antagonize cortisol in supplement form. Note that in the study (**), PS levels lowered in favor of PC and PE, and this actually suggests PS synthesis might need to be propped up when SCD1 is antagonized, though this is going out on a limb

I suppose there should be a role for the PTDSS1 enzyme (PC->PS via base exchange), but I don't know factually by which phospholipid synthesis pathway the C18:0 PS predominantly forms through. That's something to research, I guess. But PTDSS1 is a candidate to explain the link between (**) and (***), even though this is cross-BBB stuff.

Some SCD1 agonists/antagonists:
https://www.sciencedirect.com/science/article/pii/S0300908410002841
High carbohydrate diet, insulin, peroxisome proliferators and cholesterol were identified as positive effectors of SCD1 transcription whereas, triiodothyronine (T3), estrogen, PUFAs and leptin were described as inhibitors. Numerous transcription factors bind to the SCD1 promoter suggesting a fine regulation of SCD1 expression. This includes SREBP-1c, LXR, PPAR-a, C/EBP-a, NF-1, NF-Y, AP-1, Sp1, TR and PGC1-a (Fig. 1).

SCD1 antagonists:
Thyroid (https://www.sciencedirect.com/science/article/pii/S0006291X97965505)
PUFA - both long-chain omega-3 and omega-6 (Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol https://www.sciencedirect.com/science/article/pii/S0300908410002841 Dietary cholesterol opposes PUFA-mediated repression of the stearoyl-CoA desaturase-1 gene by SREBP-1 independent mechanism)
Leptin (Leptin and the control of metabolism: role for stearoyl-CoA desaturase-1 (SCD-1). - PubMed - NCBI)
Estrogen, but might not be straightforward (https://www.sciencedirect.com/science/article/pii/S0300908410002841)

SCD1 agonists:
Cholesterol, liver LXR (Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol http://www.jlr.org/content/43/10/1750.long)
PPARgamma agonists (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582575/)
PPARalpha agonists **** (https://www.pnas.org/content/pnas/93/18/9443.full.pdf https://www.hindawi.com/journals/ppar/2010/612089/)
Methionine, homocysteine, but especially cysteine (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999932/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498306/)
Serine (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495377/), maybe sarcosine?
Fructose (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495377/)
SREBP1 agonists, and usually mTorC1 agonists through it (https://www.tandfonline.com/doi/pdf/10.4161/auto.27003)
Androgens (http://www.biochemj.org/content/263/3/897)
Possibly vitamin A, not straightforward (https://www.sciencedirect.com/science/article/pii/S0006291X97960708)
Betaine, and therefore choline to an extent (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621752/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834435/)
Estrogen, possibly in some circumstances (http://www.jlr.org/content/40/9/1549.full)

**** PPARalpha (semi-)surprisingly, through SREBP1 and a complex mechanism, can induce SCD1:
https://www.pnas.org/content/93/18/9443
Peroxisome proliferators cause an influx of fatty acids, providing an immediate supply of PUFAs. However, PUFAs are preferentially broken down by peroxisomal 13-oxidation (33), causing a depletion of these PUFAs. Under conditions of essential fatty acid deficiency, SCD is activated, because it catalyzes the synthesis of the only unsaturated fatty acids that mammals can synthesize de novo. Therefore, the induction of SCD may be necessary to compensate for a lack of PUFAs in the membrane and to enhance phospholipid biosynthesis. Previous studies have shown that clofibrate results in an increase in 18:1 found in phosphatidylcholine (15), supporting this hypothesis.
This describes a mechanism by which local PUFA deficiency induces compensatory desaturase activity.
In most cases PPARalpha is desirable. You might theoretically counter its effect on SCD1 using omega-3/linolenic acid.
 

Terma

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Here is something quite relevant to this thread:
Phosphatidylserine is a critical modulator for Akt activation

PI3K/Akt is of course critical for insulin signaling, and PS is highest in the brain (the most abundance species is 18:0,22:6-PS or stearic acid + DHA tails). More info in this excellent article:
Phosphatidylserine in the Brain: Metabolism and Function

Note that 18:0,18:1-PS (stearic, oleic) is in fact already the second-most abundant PS species in the mouse brain after 18:0,22:6-PS (stearic, DHA), see Table 3:
Phosphatidylserine in the Brain: Metabolism and Function
 
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Broken man

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Here is something quite relevant to this thread:
Phosphatidylserine is a critical modulator for Akt activation

PI3K/Akt is of course critical for insulin signaling, and PS is highest in the brain (the most abundance species is 18:0,22:6-PS or stearic acid + DHA tails). More info in this excellent article:
Phosphatidylserine in the Brain: Metabolism and Function

Note that 18:0,18:1-PS (stearic, oleic) is in fact already the second-most abundant PS species in the mouse brain after 18:0,22:6-PS (stearic, DHA), see Table 3:
Phosphatidylserine in the Brain: Metabolism and Function
Thank you So much for your detailed reply, IT seems to me So much hardcore that my brain Will take break for week to understand it :D.
 
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paymanz

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Physiological roles of taurine in heart and muscle | Journal of Biomedical Science | Full Text
One of the most prominent taurine-mediated changes in membrane function was found to be the inhibition of phospholipid N-methyltransferase, an enzyme that catalyzes the conversion of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) [75]. This reaction is important because taurine levels regulate the ethanolamine:choline ratio of some membranes [76]. In the biological membrane, PE is preferentially localized to the outer membrane leaflet where it assumes a bilayer structure while PC is a hexagonal former and is preferentially localized to the inner leaflet of the membrane. Thus, changes in the PE/PC ratio have a dramatic influence on the structure of biological membranes, which in turn alters both membrane fluidity and the activity of membrane enzymes and transporters
 

Terma

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The one they cited, good find:
Sci-Hub | Interaction of Taurine with Methionine. Journal of Cardiovascular Pharmacology, 18(2), 224–230 | 10.1097/00005344-199108000-00008
Perfusion of isolated, working rat heart with buffer containing 300 microM methionine in the presence of 2.5 U/L insulin led to a 15% decrease in cardiac work and a four-fold decrease in sarcolemmal Na(+)-Ca2+ exchange activity. These effects of methionine were largely prevented by inclusion of 10 mM taurine in the buffer supplemented with methionine and insulin. Taurine also reduced the extent of 3H-methyl group incorporation from radioactive methionine into myocardial phospholipids by approximately 45%. Assays of sarcolemmal phospholipid methyltransferase activity at catalytic sites I, II, and III revealed that taurine inhibited N-methylation activity approximately 30%. The data imply that the ability of taurine to modulate myocardial contraction and calcium transport may be related to taurine-mediated inhibition of phospholipid N-methylation.
 
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