The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism (2013 China) Via the FXR receptor, ivermectin reduces serum glucose and cholesterol levels in wild mice (NOT directly covid-related)

[-] DreadPyriteRoberts | 1 points | Jan 04 2021 02:00:38

From [here](https://www.wikipathways.org/index.php/Pathway:WP2879#:~:text=The%20farnesoid%20X%20receptor%20(FXR,via%20the%20CPTAC%20Assay%20Portal):

The farnesoid X receptor (FXR, a.k.a. NR1H4) is a nuclear receptor that responds to levels of bile acids present in the body and regulates many processes related to bile acids synthesis and transport.

From here:

FXR is expressed at high levels in the liver and intestine. Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Similar to other nuclear receptors, when activated, FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes.[6]

One of the primary functions of FXR activation is the suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, FXR induces expression of small heterodimer partner (SHP), which then functions to inhibit transcription of the CYP7A1 gene. In this way, a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are already high.

FXR has also been found to be important in regulation of hepatic triglyceride levels.[7] Specifically, FXR activation suppresses lipogenesis and promotes free fatty acid oxidation by PPARα activation.[7] Studies have also shown the FXR to regulate the expression and activity of epithelial transport proteins involved in fluid homeostasis in the intestine, such as the cystic fibrosis transmembrane conductance regulator (CFTR).[8]

Activation of FXR in diabetic mice reduces plasma glucose and improves insulin sensitivity, whereas inactivation of FXR has the opposite effect.[7]

So apparently this result has not (yet) been observed in humans?

[-] luisvel | 1 points | Jan 04 2021 02:45:03

Well... it IS highly Covid related apparently.

Molecules that reduce cholesterol or disrupt ACE2 localization with viral entry points or furin localization in the producer cells, may reduce the severity of COVID19 in obese patients.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263494/