Genetic background strongly influences the impact of carrying the Thr92Ala-DIO2 polymorphism in the male mouse

[helvella]

Are you male?

Are you a mouse?

Do you carry the Thr92Ala-DIO2 allele?

Can you wait for the publication of this paper?

Can you wait for the human version of this trial?

And do you consider it necessary to wait for the eventual publication of the human trial before considering T3?

It is undoubtedly good news that this research is progressing. But, realistically, we have to decide what we need right now and go for it. (With due caution, of course.) And just wave this study to try to justify getting prescribed T3. At least it suggests that there could be a sound scientific reason thus challenges the "never T3" brigade.

Endocrinology. 2024 Jun 5:bqae064.

doi: 10.1210/endocr/bqae064. Online ahead of print.

Genetic background strongly influences the impact of carrying the Thr92Ala-DIO2 polymorphism in the male mouse

Guilherme Gabriel de Almeida 1 , Anaysa P Bolin 2 , Alice Batistuzzo 1 , Tatiana Fonseca 1 , Miriam O Ribero 3 , Antonio C Bianco 1

PMID: 38836615 DOI: 10.1210/endocr/bqae064

Abstract

About half of the world population carries at least one allele of the Ala92-DIO2, which slows down the activity of the type 2 deiodinase (D2), the enzyme that activates T4 to T3. Carrying the Ala92-DIO2 allele has been associated with increased BMI and insulin resistance, but this has not been reproduced in all populations. To test if the genetic background affects the impact of this polymorphism, here we studied the genetically distant C57Bl/6J (B6) and FVB/N (FVB) mice carrying the Ala92-Dio2 allele as compared to control mice carrying the Thr92-Dio2 allele. Whereas B6-Ala92-Dio2 and B6-Thr92-Dio2 mice⸺fed chow or high fat diet⸺behaved metabolically similar in studies using indirect calorimetry, glucose- and insulin-tolerance tests, and measuring white adipose tissue (WAT) weight and liver steatosis, major differences were observed between FVB-Ala92-Dio2 and FVB-Thr92-Dio2 mice. Carrying the Ala92-Dio2 allele (on a chow diet) resulted in hypercholesterolemia, smaller WAT pads, hepatomegaly, steatosis, and transcriptome changes in the interscapular brown adipose tissue (iBAT) typical of ER stress and apoptosis. Acclimatization at thermoneutrality (30°C) eliminated most of the metabolic phenotype, indicating that impaired adaptive (BAT) thermogenesis can be involved. In conclusion, the metabolic impact of carrying the Ala92-Dio2 allele depends greatly on the genetic background of the mouse, varying from no phenotype in B6 mice to a major phenotype in FVB mice. These results will help the planning of future clinical trials studying the Thr92Ala-DIO2 polymorphism and may explain why some of the clinical studies performed in different populations across the globe have obtained inconsistent results.

Keywords: deiodinases; lipids; steatosis; thyroid hormone.

Only pre-publication abstract available:

pubmed.ncbi.nlm.nih.gov/388...

[Regenallotment]

hooray (for male mice) 👏🤣 definitely a tiny weeny mouse step forward for all mammals 🙏🌱

[FallingInReverse]

Are you male?

Are you a mouse?

😂🐭🤣🐁😂🐭🤣🐁😂

[FallingInReverse]

Love the connection also to cholesterol issues, insulin resistance and BMI. I wonder if they make the distinction between the DIO gene vs the resulting low T3 as the cause?

When I got my T3, my doctor said “well, 50 mcgs of Levo isnt making you feel better, let’s try something experimental. “ I had been googling it all as well, and when I found internet sources on T3 it certainly did feel experimental. There was one I think 10 year old paper I found, and I think I read some Paul Robeson web pages about T3 mono.

I look back now and realize how completely misunderstood it all is… like - you read about the Dio gene, and we know the role of T3 in our bodies, and yet, it’s still hidden away. So weird, I don’t get it.

[helvella Administrator Thyroid UK in reply to FallingInReverse]

Yet T3 has been around since 1956!

Early on, it was even discussed as the first line treatment of choice. Start T3 because it acts fast, and dose adjustment is much quicker. Once a decent dose has been reached, switch over to levothyroxine (not sure if a combination was considered in this context).

[ThyroidieGriaffe]

Thanks for sharing... signed Micky Mouse