Thyroid-stimulating hormone (TSH) regulates hepatic bile acid homeostasis via SREBP-2/HNF-4α/CYP7A1 axis

[helvella]

Just a little something to think about while cooking or eating turkey. Or nut roast. Or whatever else.

J Hepatol. 2014 Dec 19. pii: S0168-8278(14)00924-6. doi: 10.1016/j.jhep.2014.12.006. [Epub ahead of print]

Thyroid-stimulating hormone (TSH) regulates hepatic bile acid homeostasis via SREBP-2/HNF-4α/CYP7A1 axis.

Song Y1, Xu C1, Shao S1, Liu J2, Xing W1, Xu J1, Qin C3, Li C2, Hu B1, Yi S4, Xia X5, Zhang H1, Zhang X1, Wang T1, Pan W1, Yu C1, Wang Q6, Lin X6, Wang L7, Gao L8, Zhao J9.

Author information

Abstract

BACKGROUND & AIMS:

Bile acids (BAs) play a crucial role in dietary fat digestion and in the regulation of lipid, glucose, and energy metabolism. Thyroid-stimulating hormone (TSH) is a hormone produced by the anterior pituitary gland that has been shown to directly regulate several metabolic pathways. However, the impact of TSH on BA homeostasis remains largely unknown.

METHODS:

We analyzed serum BA and TSH levels in healthy volunteers under strict control of caloric intake. Thyroidectomized rats were administered thyroxine and injected with different doses of TSH. Tshr (-/-) mice were supplemented with thyroxine, and C57BL/6 mice were injected with Tshr-siRNA via the tail vein. The serum BA levels, BA pool size, and fecal BA excretion rate were measured. The regulation of SREBP-2, HNF-4α, and CYP7A1 by TSH were analyzed using luciferase reporter, RNAi, EMSA, and CHIP assays.

RESULTS:

A negative correlation was observed between the serum levels of TSH and the serum BA levels in healthy volunteers. TSH administration led to a decrease in BA content and CYP7A1 activity in thyroidectomized rats supplemented with thyroxine. When Tshr was silenced in mice, the BA pool size, fecal BA excretion rate, and serum BA levels all increased. Additionally, we found that HNF-4α acts as a critical molecule through which TSH represses CYP7A1 activity. We further confirmed that the accumulation of mature SREBP-2 protein can impair the capacity of nuclear HNF-4α to bind to the CYP7A1 promoter, a mechanism that appears to mediate the effects of TSH.

CONCLUSIONS:

TSH represses hepatic BA synthesis via a SREBP-2/HNF-4α/CYP7A1 signaling pathway. This finding strongly supports the notion that TSH is an important pathophysiological regulator of liver BA homeostasis independent of thyroid hormones.

Copyright © 2014. Published by Elsevier B.V.

KEYWORDS:

Bile acids; CYP7A1; HNF-4α; SREBP-2; Thyroid-stimulating hormone

PMID:

25533663

ncbi.nlm.nih.gov/pubmed/255...

Rod

[Clutter]

Rod, this won't inhibit me from eating my own weight in turkey and roast potatoes. I'll avoid the little green balls of death though.

[gabkad in reply to Clutter]

Clutter, that's not terribly awe inspiring. When you eat MY weight in turkey and roast potatoes, now that'll be something. LOL!

[Hidden in reply to gabkad]

Happy Christmas!! .............The turkey is in the oven And I'm sitting here with a cuppa with a few mental pictures building...........Hey ...that's what we need ....A Poste Christmas Gallery of Cartoon Characters stuffed with Christmas Fare all anticipating next week's visit to the Endo !

Enjoy your day everyone.xx

[greygoose]

Not very inspiring, is it! The one thing we really don't need is another arguement against suppressed TSH! Besides, where does that leave all of us with no gall bladder?

Merry Christmas, anyway! lol No turkey for me, we have an Indonesian dish called Bul Gogi (spelling?) where by everyone cooks their own marinaded thinly sliced beef at the table. All I have to do is cook the rice! Excellant! lol

[helvella Administrator Thyroid UK in reply to greygoose]

Not sure it says that. High TSH seems to suppress BA - perhaps it is an argument against leaving TSH to get to 10 before treatment?

Mind, I'd like to know what the full paper says and to discuss it before coming to any firm conclusions.

But if it is to be used to bash us into TSH conformance, better we know, hence my posting.

Enjoy!

[greygoose in reply to helvella]

Oh, absolutely! We need to know it all because nobody else does! Wouldn't that be great if it did argue against letting the TSH rise?!? Will read it more carefully after Christmas, as I'm just sitting here waiting for the guests to arrive and not really concentrating!

Enjoy, too - whatever it is!

[Jazzw]

So - the higher the TSH, the lower your bile acid? Is that what it's saying?

Well, that would actually explain why hypothyroid folk develop gallbladder problems, wouldn't it!

Or have I read that the wrong way around?

[Flower3]

I don't understand what this means..Could this also be why hypothyroid people often have digestion problems as you need bile to digest food?

[helvella Administrator Thyroid UK in reply to Flower3]

I posted it while still not sure what it means myself!

Hoping others might understand and fill in our understanding.

[cc120]

That doesn't surprise me as my digestive capabilities seemed to diminish in pace with my TSH increase.

[Flower3 in reply to cc120]

Maybe it's a combination of slow metabolism and not enough bile acid, that combination is horror for our digestion.

I hope somebody can explain this in a really easy way.

[cc120 in reply to Flower3]

My GP medicated with Gaviscon for high stomach acid for years. Finally, I a member on here suggested I might have low stomach acid. I started Betaine Hydrochloride & Pepsin Capsules and noticed on the first day a considerable improvement in reflux, digestion. I now take 1 or 2 at every meal. Buy from gnc.co.uk, Contains: Betaine Hydrochloride- 648 mg- Pepsin- 130mg.

[Spareribs]

Hubby had omeprazole, grr... - but since (he) discovered (apple) cider vinegar he's fine now...