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[LGMD2A]

Hello,

 

A friend of mine refered me to this forum. I am Limb-Girdle Muscular Dystrophy type 2A patient (LGMD2A) and I am seeking information about possible strategies to boost PGC1Alpha with supplements or food. 

 

Some brief information about LGMD2A: it is the only type of muscular dystrophy not caused by mutation in a gene, encoding a structural protein (eg. situated in the muscle cell wall) but by proteolytic enzyme instead. "Calpain 3" exact functions in the cell are kind of a mystery yet, but a recent paper revealed that its lack in the cell is leading to failure to properly express Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1Alpha):

 

Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A (calpainopathy).

http://www.ncbi.nlm....pubmed/27005420

 

Hence mitochondria are unable to utilize lipid substrates (triacylglycerol - diacylglycerol - fatty acids) for energy production.

PGC1Alpha is quicky up-regulated in healthy muscles even after a single bout of exercise and that results in coordinated gene expression for "muscle growth and adaptation response". 

In mice with LGMD2A however it is not upregulated and the authors of the paper suggest that indeed this is the underlying disease mechanism - the muscles doesn't recover properly after exercises. Glucose metabolism pathways are not affected - indeed they are over-expressed in order to compensate for the defective lipid metabolism. Also the authors proved that failure of proper PGC1Alpha expression is unique to LGMD2A as mice with Duschene Muscular Dystrophy are expressing it properly. 

 

As a personal experience I've noticed that I am gaining extremely quickly fat tissue instead of burning it as energy. That happens with virtually every fat that I eat - saturated and unsaturated, with the notable exception of flaxseed oil. I make flaxseed oil with hydraulic press at home and I've noticed that it goes rancid within minutes, it’s very reactive. One spoon of it gives me energy for whole day, but so far I am reluctant to use it frequently due to concerns about phytoestrogens messing up with my testosterone levels.  

 

I would like to ask you about your thoughts regarding a possible link between flaxseed oil and PGC1Alpha (or lipid metabolism in general)?

My second question is about other supplements/foods that might boost PGC1Alpha activity?

[tunt01]

In my notes I have the following PGC1alpha activators scribbled down:

 

1.  Gallic Acid (Doan 2015)

2.  Telmisartan (Shiota 2012)

3.  Ursolic Acid (Bakhtiari 2015)

4.  Nicotinamide Riboside (??)

5.  Resveratrol (??)

6.  Quercetin Source

 

 

Please note that, SIRT3 is considered to be downstream of PGC1alpha (Kong 2009).  Telmisartan half-life is purported to be approximately 24 hrs, therefore if you need sustained pgc-1alpha activation, this may be a viable route.

 

In terms of flaxseed and lipid metabolism, my first thought is that alpha-linolenic acid (flax) is a ligand of ppar-alpha, ppar-beta/delta.  ppar-alpha, in particular, is involved in fatty acid oxidation and is frequently found to reduce triglycerides and symptoms of metabolic syndrome (Yari 2016), which isn't exactly what your condition seems to be, but maybe something similar.  I'm not sure.

 

I'd be curious how your situation responds to fibrates, MCT oil (does not require typical enzymes for entry into mitochondria for oxidation and is processed in the liver, not the muscles), or maybe Thiazolidinediones.  I'm not entirely sure.  Interesting situation you have.  I wonder how your lipid panel looks on a basal and postprandial basis.  You might want to get a cardiochek PA or PRIMA and look into it.

 

 

 

Doan KV, e. (2015). Gallic acid regulates body weight and glucose homeostasis through AMPK activation. - PubMed - NCBI . Ncbi.nlm.nih.gov. Retrieved 9 May 2016, from http://www.ncbi.nlm....pubmed/25356824

 

 

Kong X, e. (2009). Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. - PubMed - NCBI . Ncbi.nlm.nih.gov. Retrieved 9 May 2016, from http://www.ncbi.nlm....pubmed/20661474

 

 

Shiota A, e. (2012). Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice. - PubMed - NCBI . Ncbi.nlm.nih.gov. Retrieved 9 May 2016, from http://www.ncbi.nlm....pubmed/23137106

 

 

Bakhtiari N, e. (2015). Ursolic acid ameliorates aging-metabolic phenotype through promoting of skeletal muscle rejuvenation. - PubMed - NCBI .Ncbi.nlm.nih.gov. Retrieved 9 May 2016, from http://www.ncbi.nlm....pubmed/25976755

 

Yari, Z., Rahimlou, M., Poustchi, H., & Hekmatdoost, A. (2016). Flaxseed Supplementation in Metabolic Syndrome Management: A Pilot Randomized, Open-labeled, Controlled Study. Phytother. Res.. doi:10.1002/ptr.5635

Edited by prophets, 10 May 2016 - 12:07 AM.