Activating FXR decreases PUFA in the liver

[Mauritio]

Very interesting study showing that activating the Farnesoid X Receptor results in lower levels of MUFA and PUFA in the liver.
(Farnesoid X receptor - Wikipedia)

Lowers levels of MUFA are brought on by downregulating genes like SCD1.
"Elevated expression levels of SCD1 is found to be correlated with obesity [20] and tumor malignancy.[21]"
(Stearoyl-CoA desaturase-1 - Wikipedia)

Lower levels of PUFA were caused by lower absorption of it from the intestines.

Interestingly, levels of saturated fats were not affected by activating FXR, thereby shifting the ratio of saturated:unsaturated fats in a favorable direction.

I think lower levels of PUFA (and to a lesser degree MUFA) in the liver could bring about all kinds of positive changes: better conversion of T4 to T3, less inflammation/NAFLD/NASH, better detoxification of endotoxin and estrogens,...

Activators of FXR are:
Progesterone, Pregnenolone, Ivermectin, Androsterone, Bile acids, Cafestol...


"FXR activation in mice or humans specifically reduces hepatic levels of mono- and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption."

FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption - PubMed

FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive...

pubmed.ncbi.nlm.nih.gov

 

[Jam]

Very interesting study showing activating the FX-Receptor results in lower levels of MUFA and PUFA in the liver.
(Farnesoid X receptor - Wikipedia)

Lowers levels of MUFA are brought on by downregulating genes like SCD1.
(Stearoyl-CoA desaturase-1 - Wikipedia)

Lower levels of PUFA were caused by lower absorption of it from the intestines.

I think lower levels of PUFA (and to a lesser degree MUFA) in the liver could bring about all kinds of positive changes: better conversion of T4 to T3, less inflammation/NAFLD/NASH, better detoxification of endotoxin and estrogens,...

Activators of FXR: Progesterone , pregnenolone, ivermectin, androsterone, Bile acids...


"FXR activation in mice or humans specifically reduces hepatic levels of mono- and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption."

FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption - PubMed

FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive...

pubmed.ncbi.nlm.nih.gov

Cafestol - Wikipedia

en.m.wikipedia.org

Coffee consumption has been associated with a number of effects on health and cafestol has been proposed to produce these through a number of biological actions.[4] Studies have shown that regular consumption of boiled coffee increases serum cholesterol whereas filtered coffee does not.[5] Cafestol may act as an agonist ligand for the nuclear receptor farnesoid X receptor and pregnane X receptor, blocking cholesterol homeostasis. Thus cafestol can increase cholesterol synthesis.[6]

 

[Mauritio]

Cafestol - Wikipedia

en.m.wikipedia.org

Thanks . I added cafestol.

 

[Mauritio]

Cafestol - Wikipedia

en.m.wikipedia.org

Did you ever try cafestol?

 

[Jam]

Did you ever try cafestol?

Not outside of coffee.

 

[Mauritio]

Not outside of coffee.

Ok, thanks anyway. I'm looking for new FXR agonists ,but maybe Ill just try taurine again.

 

[youngsinatra]

Seems like promoting bile flow helps with everything regarding hepatotoxicity by lowering stores of fat-soluble toxins by promoting their excretion through a bowel movement.

I had huge problems with bile flow for a long time but a mix of B1 (sublingual TPP), B2, methylfolate, B12, thyroid and black coffee have been hugely helpful for me.

 

[Mauritio]

Seems like promoting bile flow helps with everything regarding hepatotoxicity by lowering stores of fat-soluble toxins by promoting their excretion through a bowel movement.

I had huge problems with bile flow for a long time but a mix of B1 (sublingual TPP), B2, methylfolate, B12, thyroid and black coffee have been hugely helpful for me.

FXR is an absolutely fascinating receptor. T3 will incrase cholesterol's conversion into bile acids, which activate FXR, so in a way T3 will also help with gallbladder and liver issues (and the many other things FXR helps with).
I have also identified bile as a major factor that influences my health. I started noticing that everything that activates the FXR (5aDHP, andorsterone,...) gives me benefits, so I'll try cafestol from instant decaf coffee next.

 

[Mauritio]

FXR's effects seem to depend to a degree on a protein called FGF19, which is a growth factor that acts in an endocrine way and helps with liver regeneration.

- Fibroblast Growth Factor 19 modulates intestinal microbiota and inflammation in presence of Farnesoid X Receptor - PubMed

 

[Mauritio]

FXR activation mediates cardioprotection via adiponectin

- Adiponectin determines farnesoid X receptor agonism-mediated cardioprotection against post-infarction remodelling and dysfunction - PubMed

 

[Mauritio]

- Farnesoid-X Receptor (FXR) as a Promising Pharmaceutical Target in Atherosclerosis - PubMed

 

[Mauritio]

Yangonin is another FXR agonist.

- Yangonin protects against cholestasis and hepatotoxity via activation of farnesoid X receptor in vivo and in vitro - PubMed
- Yangonin - Wikipedia

 

[Mauritio]

This study adds a lot of new FXR-agonists to the list. Some of them:

Agonists:
- Naringin
- farnesol
- Rutin
- Resveratrol
- Epigallocatechin-3-gallate (EGCG)
- Glutamine
- Ergosterol peroxide
- ganoderiol F
- ganodermanontriol
- Dioscin
- Salidroside
- Imperatorin
- Arctigenin
- Liquiritigenin
- Boldine
- Berberine

Antagonists:
- Stigmasterol ("a phytosterol prevalent in soy-derived parenteral nutrition lipid solutions, it was a potent antagonist of FXR according to the test of ligand-activated NR-ligand binding domains in vitro.55")
- gorgosterol
- Oleanolic acid

- Farnesoid X receptor regulators from natural products and their biological function