17 replies to this topic

[DjKrush86]

I have been struggling now with a condition for about eight years. I have recently been interested in learning about PPAR as I think it maybe driving my condition. Or rather, its signaling may be off. Hoping someone here can let me bounce some ideas off them or maybe recommend a place that may also have people weighing in on this subject. Thanks.

[tunt01]

I've read about PPARs a fair bit.  

 

One interesting review paper is:

 

Grygiel-Górniak, B. (2014). Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications – a review. Nutrition Journal,13(1), 17. doi:10.1186/1475-2891-13-17

 

One interesting video is:

 

NIH Cast - PPARs Treatment and Disease Prevention

 

[DjKrush86]

Are you familiar at all with the bile related receptors and their influence like LXR, or FXR?

[tunt01]

LXR is a nuclear receptor, but not a PPAR.  I have a decent chunk of notes on LXR and related matters.  I think I watched some presentations from Dr. Thomas Dayspring on www.lecturepad.org or on youtube.  You can search for his presentations on lipidology and LXR/RXR receptors.  He's quite good.

[DjKrush86]

Yes, I basically think that I have an issue with these receptors and their influence on PPAR signaling. 

[tunt01]

Yes, I basically think that I have an issue with these receptors and their influence on PPAR signaling. 

 

I've no idea what to make of that without any medical test results or data.  You would obviously need someone like a clinical lipidologist to evaluate it.

[DjKrush86]

OK, let me ask you this. What do you think acute ethanol exposure would do to PPAR? I am wondering if its anti-inflammatory effects may enhance PPAR-a.

[tunt01]

I'm not qualified to offer an opinion on the interaction of ethanol and ppar-alpha.  AFAIK, PPARs are involved in fatty acid breakdown and fatty acid metabolism in general (storage, etc.).

 

I suppose if a human being ingests ethanol, it converts to triglycerides and there is some kind of PPAR deficiency it will result in a poor handling of the triglycerides.  But it's hard for me to say what if anything that will entail.  There would have to be some kind of physiological evidence in the form of hepatic steatosis (fatty liver disease).

[DjKrush86]

Do you know what the relationship is between ppar a/y with ppar delta? I have gathered that Ppar delta may inhibit their actions. 

 

 

I'm not qualified to offer an opinion on the interaction of ethanol and ppar-alpha.  AFAIK, PPARs are involved in fatty acid breakdown and fatty acid metabolism in general (storage, etc.).

 

I suppose if a human being ingests ethanol, it converts to triglycerides and there is some kind of PPAR deficiency it will result in a poor handling of the triglycerides.  But it's hard for me to say what if anything that will entail.  There would have to be some kind of physiological evidence in the form of hepatic steatosis (fatty liver disease).

 

[tunt01]

Read the material provided

Sent from my XT1575 using Tapatalk

[DjKrush86]

In your reading did you come across any good agents that increase ppar-a proliferation without increasing ppar-y? Or any agents that block nf-kappa-b from binding with ppar alpha DNA signaling?

 

 

Read the material provided

Sent from my XT1575 using Tapatalk

 

[tunt01]

We describe two novel, potent oxybenzylglycine PPARalpha-selective agonists, BMS-687453 [N-[[3-[[2-(4-chlorophenyl)-5-methyl-4-oxazolyl]methoxy]phenyl]methyl]-N-(methoxycarbonyl)-glycine] and BMS-711939 N-[[5-[[2-(4-chlorophenyl)-5-methyl-4-oxazolyl]methoxy]-2-fluorophenyl]methyl]-N-(methoxycarbonyl)-glycine], that robustly increase apolipoprotein (Apo) A1 and high-density lipoprotein cholesterol in human ApoA1 transgenic mice and lower low-density lipoprotein-cholesterol and triglycerides in fat-fed hamsters.

 

 

 

 

Mukherjee R, e. (2008). Novel peroxisome proliferator-activated receptor alpha agonists lower low-density lipoprotein and triglycerides, raise high-density lipoprotein, an... - PubMed - NCBI . Ncbi.nlm.nih.gov. Retrieved 2 January 2017, from https://www.ncbi.nlm...pubmed/18799592

[DjKrush86]

You feel LXR agonism would be a superior route?

[tunt01]

You feel LXR agonism would be a superior route?

 

Impossible for me to say.  1)  I'm not a doctor and I've still got a long way before I really understand this area.   2)  I don't even know what kind of metabolic issue you are talking about.  I only provided these links and information as an overview of PPARs.  I'm not even sure what you are trying to address other than to under PPARs.

 

Some kind of fibrate is typically the answer for a pharmacologic activation of PPARs.  But fish oil (PUFAs), niacin other approaches are possible.  It just depends on what is going on and it's impossible for me to say with any kind of certitude.

[chung_pao]

What is your:
Condition/problem?
Hypotheses?

Main objective / current target or method to correct it?

What is the problem and what do you want to do about it?


I am in the same situation.
Disease occurred 3 years ago.
Still struggling and testing to correct it.

PPAR's may be involved. Especially PPAR gamma.
Other receptors of interest:
RAR. CAR. PXR. AHR.

[chung_pao]

For PPAR alpha activation, I would look at cAMP.

Try to increase it through sustainable means.

Fasting. Exercise. Low carb and possibly calorie diet.
Minimize insulin.

But what is the problem?
Looking only at mechanisms, we can't assist you.

[maxwatt]

Interesting writeup here https://www.ncbi.nlm.../table/tbl0005/

But it deals mostly with PPAR-gamma agonists.
 

PPAR-delta seems to improve mitochondrial number, and may reduce weight gain. The effect on endurance is similar to exercise.  PPARdelta agonists such as AiCAR have been banned in sport for this reason.  Micardis is an angiotensin reuptake inhibitor that also activates PPAR-delta. It causes fewer respiratory problems than other angiotensin reuptake inhibitors.  But can still cause cough, and possibly lung cancer though this is debatable.

 

I believe PPAR-alpha agonists such as fibrates tend to induce weight gain, whereas PPAR-gamma agonists do not. Both tend to reduce insulin resistance. 

Luteolin and resveratrol are two substances that activate both of these PPARs.

 

I hope you find what you need.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

i n

 

 

[PhaQ]

PPAR-delta seems to improve mitochondrial number, and may reduce weight gain. The effect on endurance is similar to exercise. PPARdelta agonists such as AiCAR have been banned in sport for this reason. Micardis is an angiotensin reuptake inhibitor that also activates PPAR-delta. It causes fewer respiratory problems than other angiotensin reuptake inhibitors. But can still cause cough, and possibly lung cancer though this is debatable.

I believe PPAR-alpha agonists such as fibrates tend to induce weight gain, whereas PPAR-gamma agonists do not. Both tend to reduce insulin resistance.

You got that mixed up. Fibrates and PPAR-alpha agonists tend to cause weight loss. PPAR-gamma agonists tend to cause not just weight gain, but adipogenesis as well.