GDF15 linked to maternal risk of nausea and vomiting during pregnancy 2023 Fejzo et al (hyperemesis gravidarum - morning sickness in pregnancy)

Extreme morning sickness? Scientists finally pinpoint a possible cause

"Researchers have pinpointed a hormone released by growing fetuses that might cause a debilitating form of morning sickness. Women who are more sensitive to the hormone, which increases during early pregnancy, might be at greater risk of experiencing a severe form of nausea and vomiting, called hyperemesis gravidarum, according to their study.

“For the first time, hyperemesis gravidarum could be addressed at the root cause, rather than merely alleviating its symptoms,” says Tito Borner, a physiologist at the University of Pennsylvania. The work was published on 13 December in Nature1.

The finding could also open avenues for treatment. “We now have a clear view of what may cause this problem and a route for both treatment and prevention,” says study co-author Stephen O’Rahilly, a metabolism researcher at the University of Cambridge, UK."

https://www.nature.com/articles/d41586-023-03982-8

 

Of possible interest is this study, Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome, 2019, Melvin, Lacerda, Nacul et al

 

Metformin being postulated as a potential treatment on radio today.

 

See also recent review Intracellular to Interorgan Mitochondrial Communication in Striated Muscle in Health and Disease (2023, Endocrine Reviews), authors including Rob Wüst —

 

Thought this also seemed interesting,
GDF15 promotes weight loss by enhancing energy expenditure in muscle, 2023, Wang et al

Abstract
Caloric restriction that promotes weight loss is an effective strategy for treating non-alcoholic fatty liver disease and improving insulin sensitivity in people with type 2 diabetes1. Despite its effectiveness, in most individuals, weight loss is usually not maintained partly due to physiological adaptations that suppress energy expenditure, a process known as adaptive thermogenesis, the mechanistic underpinnings of which are unclear2,3. Treatment of rodents fed a high-fat diet with recombinant growth differentiating factor 15 (GDF15) reduces obesity and improves glycaemic control through glial-cell-derived neurotrophic factor family receptor α-like (GFRAL)-dependent suppression of food intake4,5,6,7. Here we find that, in addition to suppressing appetite, GDF15 counteracts compensatory reductions in energy expenditure, eliciting greater weight loss and reductions in non-alcoholic fatty liver disease (NAFLD) compared to caloric restriction alone. This effect of GDF15 to maintain energy expenditure during calorie restriction requires a GFRAL–β-adrenergic-dependent signalling axis that increases fatty acid oxidation and calcium futile cycling in the skeletal muscle of mice. These data indicate that therapeutic targeting of the GDF15–GFRAL pathway may be useful for maintaining energy expenditure in skeletal muscle during caloric restriction.

 

It's also worth noting that this finding was foreshadowed by an earlier GWAS study via 23andMe —

Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum (2018)
Fejzo, Marlena S.; Sazonova, Olga V.; Sathirapongsasuti, J. Fah; Hallgrímsdóttir, Ingileif B.; Vacic, Vladimir; MacGibbon, Kimber W.; Schoenberg, Frederic P.; Mancuso, Nicholas; Slamon, Dennis J.; Mullin, Patrick M.

Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3–2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complications. Two loci, chr19p13.11 and chr4q12, are genome-wide significant (p < 5 × 10−8 ) in both association scans and are replicated in an independent cohort. The genes implicated at these two loci are GDF15 and IGFBP7 respectively, both known to be involved in placentation, appetite, and cachexia. While proving the casual roles of GDF15 and IGFBP7 in nausea and vomiting of pregnancy requires further study, this GWAS provides insights into the genetic risk factors contributing to the disease.

Link | PDF (Nature Communications)

They concluded —

 

I just listened to the author interviewed on Radio NZ today and immediately came here to check if her findings had been discussed. My thought was that could this be relevant to those with severe MECFS who experience extreme nausea & vomiting. It is fascinating.

 

https://www.rnz.co.nz/national/prog...-morning-sickness-so-she-discovered-the-cause

 

This is a 20 minute listen and the backstory is highly relevant to the historical and current ME/CFS research situation. Following her discovery (against the wind and tide of grant reviewers and medical misogyny) she now hopes for treatment trials. One of those is using metformin to increase GDF15 levels prior to pregnancy to de-sensitise Mum prior to the fetus producing it.

(Edit: sync-post with Hutan)

 

We don't know enough about GDF15 but it sounds as if it's not as simple as too much or too little. A few passages relating to GDF15 in ME/LC or unrelated papers.

Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts (2023, Science Translational Medicine) —

Intracellular to Interorgan Mitochondrial Communication in Striated Muscle in Health and Disease (2023, Endocrine Reviews) —

Implications of mitochondrial fusion and fission in skeletal muscle mass and health (2023, Seminars in Cell & Developmental Biology) —

 

I don’t have any experience of pregnancy but I will say nausea is a major ME/CFS symptom for me triggered by exertion. Very embarrassing in public especially.

This thread is horrifying overall. Without even reading the original article I just knew some BPSer was going to say that it’s all due to subconscious fear of pregnancy.

 

I presume the idea would be to stop metformin during the pregnancy itself, once maternal baseline GDF15 levels have been elevated.

 

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