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Are Circulating FGF21 and NT-proBNP promising novel biomarkers in ME/CFS, 2020, Joan Charles Domingo et al
DMissa
Senior Member (Voting Rights)
Possibly but not necessarily. You can have gene products upregulated at the protein level with reduced or unchanged mRNA levels. There may also be nothing wrong with the gene itself. Depends on how exactly the upregulation might be occurring.
Forbin
Senior Member (Voting Rights)
I don't know if this relates, but one of the weird symptoms I noticed when I first became ill was that my heart would start pounding within five to ten minutes of eating anything containing a lot of carbohydrates, like bread. It was worse if I ate something noticeably sweet, like ice cream.
About a year later, I had a massive reaction to drinking a can of Cherry Coca Cola on an empty stomach. I developed a pounding heart, flushed face and chest, massive sweating, having to get up every five minutes to urinate (a lot), and generally felt like death for about an hour. Then it gradually abated.
I never had experienced anything like that prior to MECFS. It took awhile, but I gradually narrowed down the source of that major reaction to the then relatively new sweetener "High Fructose Corn Syrup" (HFCS).
Since then, I've always suspected that MECFS had somehow screwed up my sugar metabolism, possibly disposing me to a sort of hypoglycemic crash followed by a rush of adrenalin..
I did have at least three glucose tolerance tests back then; they were all negative. However, during each, after a while my heart would start to pound a bit and I would feel somewhat flushed and clammy. The people doing the test seemed to think that the test was not catching these periods due the lengthy intervals between blood draws. I really should have requested that they take a blood draw while I was feeling these symptoms, but I didn't want to tell them how to do their job.
Anyway, whether this was a cause or an effect of ME is beyond me. It did improve over time, but only after my other symptoms had already shown some improvement. I still won't knowingly go near anything with HFCS in it.
About a year later, I had a massive reaction to drinking a can of Cherry Coca Cola on an empty stomach. I developed a pounding heart, flushed face and chest, massive sweating, having to get up every five minutes to urinate (a lot), and generally felt like death for about an hour. Then it gradually abated.
I never had experienced anything like that prior to MECFS. It took awhile, but I gradually narrowed down the source of that major reaction to the then relatively new sweetener "High Fructose Corn Syrup" (HFCS).
Since then, I've always suspected that MECFS had somehow screwed up my sugar metabolism, possibly disposing me to a sort of hypoglycemic crash followed by a rush of adrenalin..
I did have at least three glucose tolerance tests back then; they were all negative. However, during each, after a while my heart would start to pound a bit and I would feel somewhat flushed and clammy. The people doing the test seemed to think that the test was not catching these periods due the lengthy intervals between blood draws. I really should have requested that they take a blood draw while I was feeling these symptoms, but I didn't want to tell them how to do their job.
Anyway, whether this was a cause or an effect of ME is beyond me. It did improve over time, but only after my other symptoms had already shown some improvement. I still won't knowingly go near anything with HFCS in it.
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I'm guessing that something which is not cleared/consumed at the normal rate would be present at higher levels i.e. since it accumulates. So yes increased production is not necessary.
Chris Armstrong, & Fluge and Mella, demonstrated lower levels of certain amino acids --- presumed to be the result of increased consumption (for cellular energy). In that case there was an change to the expression of an enzyme (PDH?) and the associated RNA? From (unreliable) memory/understanding ---
[EDIT - text added] Excuse the slightly abstract addition here!
There's a slightly interesting GWAS link (in ME) i.e. to protein metabolism [Armstrong, Fluge --]:
"Ornithine Transporter type 1 protein that transports ornithine (as well as lysine and arginine) across the inner membrane of mitochondria to the mitochondrial matrix"*.
So maybe GWAS, and microRNA levels, can turn up clues i.e. if the hypothesis in this paper is valid.
*https://watermark.silverchair.com/d...TEimUfKHCyYvzbfElHtQduTM83OXZsnH0scOgl5d_BBBB
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Assays for FGF21 can be done in two ways: total and bioactive. It is possible to measure the central portion of the protein and get a normal or high result. If the protein has been deactivated (e.g. by FAP) with proteolysis of its C-terminus it could be functionally low.
I've posted some relevant papers under the fgf21 tag.
I've posted some relevant papers under the fgf21 tag.
See also thread IIMEC15 - Alain Moreau, with discussion on FGF21 in his presentation at 27:03.
DMissa
Senior Member (Voting Rights)
Sorry that i saw this so late, I don't keep good track of my s4me notifications and rarely have time for a thorough browse.
My recollection was that fluge/mella did non-cellular metabolomics (serum or plasma, whichever one) and PBMC RNA measurements to complement their ideas. I don't think Chris's work had any expression data from memory. So some aligning evidence but probably nothing functionally definitive yet I would say. Good work but would probably need more detailed follow-up. Transcript-level expression of a gene of interest in one particular circulating cell population would probably not be enough to explain altered levels of a metabolite related to that gene product, in circulating blood/serum/plasma, by itself. There are countless things contributing to metabolite levels in blood.
Actually am working with Chris atm to continue teasing out this angle. Slow going because I'm pretty overloaded atm but it's probably my favourite project that I am involved with. Hopefully stuff to publish sooner than later for you all to see... plugging away at it.