The PPAR dilemma  

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Nandi
(@nandi)
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19/11/2018 6:24 am  

Things start to get complicated.

FASEB J. 2004 Jul 9 [Epub ahead of print] Related Articles, Links

PPARbeta/delta potentiates PPARgamma-stimulated adipocyte differentiation.

Matsusue K, Peters JM, Gonzalez FJ.

It is well established that peroxisome proliferator-activated receptor-gamma (PPARgamma) has a critical role in modulating adipocyte differentiation based on gain-of-function and loss-of-function experiments. However, recent gain-of-function experiments suggest that PPARbeta may also have a role in mediating adipocyte differentiation. Because ligands for PPARs can activate more than one receptor isoform, the specific role of PPARbeta in adipocyte differentiation was examined using PPARbeta-null adipocytes. Wild-type adipocytes accumulate lipids in response to differentiation signaling induced from standard differentiation medium, and this effect is significantly reduced in PPARbeta-null adipocytes. The addition of the PPARbeta ligand L165041 to the standard differentiation medium causes enhanced adipocyte differentiation and lipid accumulation, and this effect is diminished in adipocytes lacking expression of PPARbeta. Treatment of wild-type adipocytes with the PPARgamma ligand troglitazone causes accelerated adipocyte differentiation and lipid accumulation, and this effect is marginally reduced in PPARbeta-null adipocytes. Expression patterns of mRNA markers of early and late adipocyte differentiation are consistent with the morphological and biochemical differences observed. Results from these studies demonstrate that in the absence of PPARbeta expression, adipocyte differentiation is significantly impaired, providing loss-of-function evidence supporting a role for this receptor in adipocyte differentiation. These results also demonstrate that L165041-stimulated adipocyte differentiation and lipid accumulation is mediated by PPARbeta. In addition, as the ability of troglitazone to induce adipocyte differentiation is also impaired in PPARbeta null adipocytes, this suggests that both PPARbeta and PPARgamma isoforms are required to facilitate maximal lipid accumulation and differentiation during adipogenesis.


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lylemcd
(@lylemcd)
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19/11/2018 7:16 am  

Re: Just when we thought we had it all figured out...

Posted by: Nandi12
Things start to get complicated.

FASEB J. 2004 Jul 9 [Epub ahead of print] Related Articles, Links

PPARbeta/delta potentiates PPARgamma-stimulated adipocyte differentiation.

Matsusue K, Peters JM, Gonzalez FJ.

It is well established that peroxisome proliferator-activated receptor-gamma (PPARgamma) has a critical role in modulating adipocyte differentiation based on gain-of-function and loss-of-function experiments. However, recent gain-of-function experiments suggest that PPARbeta may also have a role in mediating adipocyte differentiation. Because ligands for PPARs can activate more than one receptor isoform, the specific role of PPARbeta in adipocyte differentiation was examined using PPARbeta-null adipocytes. Wild-type adipocytes accumulate lipids in response to differentiation signaling induced from standard differentiation medium, and this effect is significantly reduced in PPARbeta-null adipocytes. The addition of the PPARbeta ligand L165041 to the standard differentiation medium causes enhanced adipocyte differentiation and lipid accumulation, and this effect is diminished in adipocytes lacking expression of PPARbeta. Treatment of wild-type adipocytes with the PPARgamma ligand troglitazone causes accelerated adipocyte differentiation and lipid accumulation, and this effect is marginally reduced in PPARbeta-null adipocytes. Expression patterns of mRNA markers of early and late adipocyte differentiation are consistent with the morphological and biochemical differences observed. Results from these studies demonstrate that in the absence of PPARbeta expression, adipocyte differentiation is significantly impaired, providing loss-of-function evidence supporting a role for this receptor in adipocyte differentiation. These results also demonstrate that L165041-stimulated adipocyte differentiation and lipid accumulation is mediated by PPARbeta. In addition, as the ability of troglitazone to induce adipocyte differentiation is also impaired in PPARbeta null adipocytes, this suggests that both PPARbeta and PPARgamma isoforms are required to facilitate maximal lipid accumulation and differentiation during adipogenesis.

I *really* think people are making far too big a deal about fat cell differentiation/hyperplasia. Yeah, fine if you get fat as a house or take the wrong drugs, it's a huge issue.

For a lean athlete, whose fat cells are nowhere close to being where they need to be to stimulate maturation of preadipocytes, the above is really a non issue as far as I'm concerned.

Lyle


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Big Cat
(@big-cat)
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Posts: 206
19/11/2018 8:13 am  

Re: Just when we thought we had it all figured out...

Posted by: Nandi12
Things start to get complicated.

FASEB J. 2004 Jul 9 [Epub ahead of print] Related Articles, Links

PPARbeta/delta potentiates PPARgamma-stimulated adipocyte differentiation.

Matsusue K, Peters JM, Gonzalez FJ.

It is well established that peroxisome proliferator-activated receptor-gamma (PPARgamma) has a critical role in modulating adipocyte differentiation based on gain-of-function and loss-of-function experiments. However, recent gain-of-function experiments suggest that PPARbeta may also have a role in mediating adipocyte differentiation. Because ligands for PPARs can activate more than one receptor isoform, the specific role of PPARbeta in adipocyte differentiation was examined using PPARbeta-null adipocytes. Wild-type adipocytes accumulate lipids in response to differentiation signaling induced from standard differentiation medium, and this effect is significantly reduced in PPARbeta-null adipocytes. The addition of the PPARbeta ligand L165041 to the standard differentiation medium causes enhanced adipocyte differentiation and lipid accumulation, and this effect is diminished in adipocytes lacking expression of PPARbeta. Treatment of wild-type adipocytes with the PPARgamma ligand troglitazone causes accelerated adipocyte differentiation and lipid accumulation, and this effect is marginally reduced in PPARbeta-null adipocytes. Expression patterns of mRNA markers of early and late adipocyte differentiation are consistent with the morphological and biochemical differences observed. Results from these studies demonstrate that in the absence of PPARbeta expression, adipocyte differentiation is significantly impaired, providing loss-of-function evidence supporting a role for this receptor in adipocyte differentiation. These results also demonstrate that L165041-stimulated adipocyte differentiation and lipid accumulation is mediated by PPARbeta. In addition, as the ability of troglitazone to induce adipocyte differentiation is also impaired in PPARbeta null adipocytes, this suggests that both PPARbeta and PPARgamma isoforms are required to facilitate maximal lipid accumulation and differentiation during adipogenesis.

Well PPARbeta stimulates proliferation, it does not seem to be a surprising conclusion that when you have more pre-adipocytes that PPARgamma differentiation leads to more differentiated adipocytes. All other studies do indicate that adipocytic differentiation by PPARbeta is entirely mediated by PPARgamma. Which is why I find it odd that they used PPARbeta null mice, but not PPARgamma null mice. Twist and turn it as you want, perhaps lyle is correct in the fact that maybe I'm stressing adipocytic differentiation too much, perhaps something else, but PPARbeta overexpression mice are resistant to obesity.

Good things come to those who weight.

The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.


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Nandi
(@nandi)
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19/11/2018 9:00 am  

I think you may have missed my point, Lyle. There's been some disappointment about the lack of intellectual content around here lately. I think this is quite significant, not in terms of the net result, but in terms of how easily we can focus on one aspect of a system without realizing that systems interact to produce sometimes surprising results.


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lylemcd
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19/11/2018 9:57 am  
Posted by: Nandi12
I think you may have missed my point, Lyle. There's been some disappointment about the lack of intellectual content around here lately. I think this is quite significant, not in terms of the net result, but in terms of how easily we can focus on one aspect of a system without realizing that systems interact to produce sometimes surprising results.

Bodybuilders being reductive or missing the big picture?
Say it isn't so.

Next thing you'll be telling me is that cortisol and estrogen aren't 'bad' and thyroid and Testosterone aren't 'good'.

Yes, I'm being sarcastic (but only partially).

I learned years ago the mistake of overly fixating on one tiny aspect of physiology without looking at the big picture (b/c I used to do it too). It's my big problem with Par and Spook over at Avant, hopefully with age/maturity they'll learn it too (doubtful since being aware of the big picture will compromise their bottom line).

It's why knockout models, while interesting and informative, don't tell you shit about the real world.

Lyle


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Deacon
(@deacon)
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19/11/2018 10:47 am  

interesating post - and some good feedback


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Big Cat
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19/11/2018 11:46 am  
Posted by: lylemcd
Bodybuilders being reductive or missing the big picture?
Say it isn't so.

Next thing you'll be telling me is that cortisol and estrogen aren't 'bad' and thyroid and testosterone aren't 'good'.

Yes, I'm being sarcastic (but only partially).

I learned years ago the mistake of overly fixating on one tiny aspect of physiology without looking at the big picture (b/c I used to do it too). It's my big problem with Par and Spook over at Avant, hopefully with age/maturity they'll learn it too (doubtful since being aware of the big picture will compromise their bottom line).

It's why knockout models, while interesting and informative, don't tell you shit about the real world.

Isn't that the mark of being really good ? Being able to fit all these seemingly insignificant bits into the bigger picture ? It's all a big puzzle, but a puzzle is never complete without all of the pieces. The problem is that people focus on the pieces too much, true enough. But that doesn't mean you shouldn't focus on the pieces at all.

Good things come to those who weight.

The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.


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djohnson459
(@djohnson459)
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Posts: 3
19/11/2018 12:40 pm  

Re: Re: The PPAR dilemma

Posted by: lylemcd
Unfortuantely, the amount of Vitamin A I suspect is necessary is likely toxic.
Think Accutane level.

A PPAR-gamma antagoinst/PPAR-delta agonist would rule for fat loss. Fish oils appears to work somewhat in that capacity, BTW.

PPAR-alpha agonism will have at most a small effect, slight increase in fat oxidation in the liver, might add up over time. Can also cause cardiac cell death.

Lyle

Is that all that PPAR-alpha agonism is capable of? Avant Labs, as you may know, recently came out with SesaThin, which is supposed to be a 'potent anti-oxidant and PPAR-alpha agonist'. According to Par Deus, it's designed to be a 'super fish oil'.

Regardless of whether it actually does what they claim, why would they bother to create a supplement that a) risks cardiac cell death and b) doesn't do much except a little FFA oxidation in the liver. Is the premise of their product completely absurd?


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natron
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19/11/2018 1:18 pm  

Re: Re: Re: The PPAR dilemma

Posted by: djohnson459
Is that all that PPAR-alpha agonism is capable of? Avant Labs, as you may know, recently came out with SesaThin, which is supposed to be a 'potent anti-oxidant and PPAR-alpha agonist'. According to Par Deus, it's designed to be a 'super fish oil'.

Regardless of whether it actually does what they claim, why would they bother to create a supplement that a) risks cardiac cell death and b) doesn't do much except a little FFA oxidation in the liver. Is the premise of their product completely absurd?

In my adventures with SesaThin, I would say it works well, and far beyond my expectations. Its effects are very noticeable, especially when your diet gets "dirty", or the addition of alcohol to ones diet.

This is a interesting thread, let's keep 'em coming.

Rick


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djohnson459
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19/11/2018 1:50 pm  

Re: Re: Re: Re: The PPAR dilemma

Posted by: natron
In my adventures with SesaThin, I would say it works well, and far beyond my expectations. Its effects are very noticeable, especially when your diet gets "dirty", or the addition of alcohol to ones diet.

This is a interesting thread, let's keep 'em coming.

Rick

I know you've mentioned that it seems to reduce bloat on a high carb intake (as others have stated), but have you verified reduced fat gain with increased caloric intake?

If it's simply a PPAR-alpha agonist, I simply cannot understand how it would be having such effects in light of Lyle's explanation of PPAR-alpha.

For it to reduce fat gain, it would either need to dramatically improve partitioning or increase TEF/uncoupling/heat. Since AFAIK, no one has ever claimed that it does the latter, and PPAR-alpha is only going to increase FFA oxidation in the liver (per Lyle), I simply cannot understand how it would be effective.


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natron
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19/11/2018 2:24 pm  

To be honest with you I do not understand exactly the science behind PPAR Alpha or PPAR Delta etc. So my comments are really to be taken with a grain of salt. All I can really say is that if you are interested in how/why this product works/doesn't work, I urge you to try it. Even if it's for a short time frame. The "anti fat gain" is noticeable in terms of body composition. In fact, a few months back I was "clean bulking", but after adding SesaThin to my regiment, I've been aolt more leanient with my diet, as well as drinking moderate amounts of alcohol. Normally, I must avoid alcohol at all cost as it wreaks havoc on my body comp. However, right now I'm down roughly 1.5 % bodyfat, and 1 lb heavier. At the time, I'm also not using any androgens. So, while it's not producing unbelievable effects, it is helping, and to a greater degree than most would merely satisfied with.

Be sure to check out MindandMuscle's next issue, as it will have the SesaThin write up, then we can take a closer look at how it supposedly works.

Maybe Par would also like to discuss the issue with us?

I should also add that IMO in really doesn't do much if anything for fat loss, just fat gain, perhaps that is a better way to label PPAR-Alpha agonist?

Rick


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Big Cat
(@big-cat)
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Posts: 206
19/11/2018 3:06 pm  

Re: Re: Re: The PPAR dilemma

Posted by: djohnson459
Is that all that PPAR-alpha agonism is capable of? Avant Labs, as you may know, recently came out with SesaThin, which is supposed to be a 'potent anti-oxidant and PPAR-alpha agonist'. According to Par Deus, it's designed to be a 'super fish oil'.

Regardless of whether it actually does what they claim, why would they bother to create a supplement that a) risks cardiac cell death and b) doesn't do much except a little FFA oxidation in the liver. Is the premise of their product completely absurd?

Avantlabs didn't 'design' sesathin. As usual Par Deus came across some studies on sesamin and thought 'shit, I can put that in a bottle and sell it'. Nothing more, nothing less. Unlike most avant products however it is inexpensive, and if you feel it works, you wouldn't be losing any money on it (which cannot be said for the majority of their other products).

Its quite possible that it exerts a multitude of beneficial effects that aren't related to PPAR-alpha at all, that may or may not be documented.

Sesamin is also a product that occurs in many foodstuffs, since sesame oil is used for lots of reasons in food preparation. I hardly think it has any nasty effects when taken in the correct dose in combination with a healthy diet. Long term PPAR-alpha activation could cause cardiac stress, but i'm assuming that's not the plan anyway. And even then, as everybody here knows, there is a world of difference between could and will.

Good things come to those who weight.

The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.


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djohnson459
(@djohnson459)
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19/11/2018 4:01 pm  

Re: Re: Re: Re: The PPAR dilemma

Posted by: Big Cat
Avantlabs didn't 'design' sesathin. As usual Par Deus came across some studies on sesamin and thought 'shit, I can put that in a bottle and sell it'. Nothing more, nothing less. Unlike most avant products however it is inexpensive, and if you feel it works, you wouldn't be losing any money on it (which cannot be said for the majority of their other products).

Its quite possible that it exerts a multitude of beneficial effects that aren't related to PPAR-alpha at all, that may or may not be documented.

Sesamin is also a product that occurs in many foodstuffs, since sesame oil is used for lots of reasons in food preparation. I hardly think it has any nasty effects when taken in the correct dose in combination with a healthy diet. Long term PPAR-alpha activation could cause cardiac stress, but i'm assuming that's not the plan anyway. And even then, as everybody here knows, there is a world of difference between could and will.

I know you and Par have a bit of an ongoing rivalry, but I have to agree with your take on the situation, particularly since a search on MedLine reveals a whole lot of rat studies but not much in vivo.

Still, the PPAR-alpha issue concerns me. Par Deus has advertised SesaThin as being both a potent PPAR-alpha agonist AND beneficial for health (cholesterol, anti-oxident properties, etc.); these suddenly seem somewhat contradictory.

Granted, I'm not even sure if there's anything that points to it being a PPAR-alpha agonist in vivo, but if it is, it seems that a) it won't really help with fat-loss and b) it could be potentially harmful.

The price certainly makes SesaThin attractive (though I wonder how cheap pure sesamin is -- I suspect there's a rather generous markup), but if it could lead to cardiac cell death (or other potential health problems), I hesitate to take the 'try it, it can't hurt' approach.

IMO, the concern about long-term health consequences is particularly notable due to the nature of the product; SesaThin, as advertised, is not just designed as a fat-loss aid, but a long-term health and wellness supplement.


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tylerdurden
(@tylerdurden)
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19/11/2018 4:53 pm  

i'm interested in this! you can give me the bibliography?
50.000 UI of vitami A for 1 month can cause problems?


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