Are Circulating FGF21 and NT-proBNP promising novel biomarkers in ME/CFS, 2020, Joan Charles Domingo et al

[John Mac]

Full title:
Are Circulating FGF21 and NT-proBNP promising novel biomarkers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, disabling, and complex multisystem illness of unknown etiology.

The protein FGF21 regulates glucose homeostasis and lipid metabolism, and the protein NT-proBNP is strongly associated with an elevated cardiovascular risk; however, little is known about their role in ME/CFS patients.

To address this gap, we explored the association between FGF21 and NT-proBNP and oxidative stress and inflammatory markers in ME/CFS.

Twenty-one ME/CFS patients and 20 matched healthy controls were included in the study.

Participants filled out validated self-reported questionnaires on their current health status covering demographic and clinical characteristics.

Plasma showed significantly decreased total antioxidant capacity and increased lipoperoxides levels (p = 0.009 and p = 0.021, respectively) in ME/CFS.

These ME/CFS patients also had significantly increased levels of inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α, and C-reactive protein (p < 0.05 for all) but not for IL-8 (p = 0.833) in ME/CFS, indicating low-grade systemic inflammation status.

Circulating FGF21 and NT-proBNP levels were significantly higher (p < 0.0001 and p = 0.005, respectively) in ME/CFS patients than in healthy controls.

Significantly positive correlations were found between NT-proBNP levels and IL-1β and IL-6 (p = 0.04 and p = 0.01) in ME/CFS patients but not between FGF21 and these cytokines.

In contrast, no significant correlations were found for either FGF21 or NT-proBNP in controls.

These findings lead to the hypothesis that elevated FGF21 and NT-proBNP levels and the association between NT-proBNP and inflammation may be promising novel diagnostic and therapeutic targets in ME/CFS.

https://www.liebertpub.com/doi/abs/10.1089/ars.2020.8230

 

[Hoopoe]

FGF21

sensitizes mice to a hibernation-like state of torpor, playing a key role in eliciting and coordinating the adaptive starvation response.

the rise in FGF21 in response to alcohol consumption inhibits further drinking.

Mice lacking FGF21 fail to fully induce PGC-1α expression in response to a prolonged fast and have impaired gluconeogenesis and ketogenesis

Source is Wikipedia

 

[MeSci]

FGF21

Animal studies are a waste of time, money and lives. I have spent years studying this.

 

[ME/CFS Skeptic]

Animal studies are a waste of time, money and lives. I have spent years studying this

Do you have any links to articles or suggested reading on this? Would be interesting to have an overview article of how often results in animal studies do or do not translate to trials in humans.

 

[Trish]

I'm confused - the abstract is about ME/CFS patients and controls. Where do the mice come in?

 

[Andy]

Where do the mice come in?

Small holes and gaps???

 

[Trish]

Small holes and gaps???

 

[Andy]

Sci hub link, https://sci-hub.se/10.1089/ars.2020.8230

Fukuda selection criteria.

Patients with ME/CFS were potentially eligible for the study if they fulfilled the 1994 CDC/Fukuda definition (5). A ME/CFS specialist diagnosed all patients who took part in the study; and also conducted all the clinical assessments of participants.

So as to remove any confounding comorbid conditions that might have influenced the data or their illness state participants were subjected to the following stringent exclusion criteria: previous or current diagnosis of acute infectious diseases in the previous 4 weeks, autoimmune disorders, multiple sclerosis, psychosis, major depression, heart disease, haematological disorders, sleep apnea or thyroid-related disorders; pregnancy or breastfeeding; smoking habit; strong hormone-related medications; and symptoms of illness that did not conform to the ME/CFS case criteria used for this study. Patients reported no other fatiguing illnesses or primary psychiatric conditions that might explain the onset of their symptoms.

 

[leokitten]

Dead end. I know it’s just my case but I had NT-proBNP measured as part of a battery of cardiovascular procedures and tests to look at my heart and the NT-proBNP results were almost zero.

Unfortunately, I was only able to get these tests in my third year or so of illness and wished I was able to examine this when I was having the heart arrhythmia issues triggered by the viral infection in the first year. They couldn’t find anything wrong with my heart after the arrhythmia mostly went away.

 

[MeSci]

Do you have any links to articles or suggested reading on this? Would be interesting to have an overview article of how often results in animal studies do or do not translate to trials in humans.

Here is a link to a PR blogpost on the subject: Cancer researcher slams requirement for animal models | Phoenix Rising ME/CFS Forums

There are several others. I can't write them now.

Animal studies almost always fail in humans.

 

[MeSci]

I'm confused - the abstract is about ME/CFS patients and controls. Where do the mice come in?

In the second post, by @Michiel Tack.

 

[Jonathan Edwards]

To be fair animal studies of normal organ function (like immune cells) have been essential to the development of a wide range of life saving treatments. What has been a huge waste of time is animal models of disease causation.

 

[shak8]

Here is a link to a PR blogpost on the subject: Cancer researcher slams requirement for animal models | Phoenix Rising ME/CFS Forums

There are several others. I can't write them now.

Animal studies almost always fail in humans.

As the virologists and immunogists on TWIV microbe TV point out:

"Mice lie and monkeys exaggerate" in experiments destined for human beings. That said, how else is one to start?

For new therapeutic molecules, basic safety and probable dosage is always tested on animals first. Lab science knows a lot about mice.

 

[J.G]

My serum FGF-21 was tested some three years ago by a London, UK immunology lab as part of a study on mitochondrial dysfunction. My serum FGF-21 levels were found to be "very low". I was told that Oxford had also seen very low levels in adult patients with MECFS. The researchers had no explanation.

 

[adambeyoncelowe]

FGF21

Very interesting.

 

[Hoopoe]

@J.G do you have poor fasting tolerance?

 

[Hutan]

Circulating FGF21 and NT-proBNP levels were significantly higher (p < 0.0001 and p = 0.005, respectively) in ME/CFS patients than in healthy controls.

My serum FGF-21 levels were found to be "very low". I was told that Oxford had also seen very low levels in adult patients with MECFS. The researchers had no explanation.

It is interesting. But these two results (both in blood) seem at odds with each other.

 

[J.G]

It is interesting. But these two results (both in blood) seem at odds with each other.

They are indeed. FGF-21 - I was told in writing - is under ongoing investigation as a potential biomarker for certain mitochondrial disorders where it is found in elevated levels. FGF-21 is also found elevated in some patients with *defined* respiratory chain defects.

Which, taken together, begs the question whether the patients in this Spanish MECFS study cohort suffer from actual core / true MECFS, or from a mitochondrial defect manifesting in a similar way. Alternatively, there could be separate ME cohorts, one with low FGF-21 of unknown etiology, one with sharply elevated FGF-21. Or perhaps PEM accounts for the difference, somehow.

 

[Hutan]

There's this 2013 study:
Mild Cold Exposure Modulates Fibroblast Growth Factor 21 (FGF21) Diurnal Rhythm in Humans: Relationship between FGF21 Levels, Lipolysis, and Cold-Induced Thermogenesis
https://academic.oup.com/jcem/article/98/1/E98/2823412

It suggests that FGF21 varies a lot over the day (at 24 degrees C: 110 pg/ml at 8 am, to 41 at 5 pm).
It also suggests that FGF21 varies with ambient temperature (lower temperature decreased variation but increased overall levels).
So, controlling for time of day and ambient temperature seems important when measuring FGF21. (I can't access the 2020 study paper, so I don't know what they did.)

Conclusions:
Mild cold exposure increased circulating FGF21 levels, predicting greater lipolysis and CIT. A small reduction in environmental temperature is sufficient to modulate FGF21 diurnal rhythm in humans, which may mediate cold-induced metabolic changes similar to those in animals.

 

[Trish]

FGF21

@strategist, can you add the source of those quotes to your post, please? They are causing some confusion.