Research Group: Mariapia Vairetti, Plinio Richelmi ,  Andrea Ferrigno, Laura G. Di Pasqua, Clarissa Berardo, Veronica Siciliano

The Farnesoid X receptor (FXR), is one of the most researched hepatic nuclear receptor. FXR receptor has a pivotal role in many pathological conditions of the gastrointestinal system, such as biliary cholangitis, non-alcoholic steatosis (NAFLD) and steatohepatitis (NASH).
We recently discovered that obeticholic acid (OCA), a newly commercialized FXR agonist, is able to modulate the hepatic metabolization and excretion of asymmetric dimethylarginine (ADMA), a methylated arginine considered a serious risk factor for cardiovascular and renal diseases, and implicated in multiorgan failure. High ADMA serum levels have been found in obese subjects and were directly correlated to insulin resistance, possibly contributing to the increased cardiovascular risk in these subjects.
In previous researches, we found that the activation of FXR receptor increases the biliary excretion of ADMA, by means of the modulation of hepatic cationic transporters. Currently, we are further investigating the role of the FXR receptor in the modulation of ADMA metabolization and excretion, the molecular mechanisms involved in the FXR-mediated alteration of the ADMA pathway, and the suitability of OCA as a novel therapy for the prevention of ADMA-related cardiovascular diseases, in subjects with metabolic syndrome and NAFLD/NASH. To accomplish this goal, we use in vitro and in vivo models of steatohepatitis, such as human hepatic cell lines cultured in lipid-enriched media, or rodents fed with high fat diets. After in vitro or in vivo treatment with agonists and antagonists of the FXR receptor, the expression of the enzymes of the ADMA pathway are evaluated by Real-Time PCR and Western-Blotting.

Recent Publications:

• Ferrigno A, Di Pasqua LG, Berardo C, Rizzo V, Richelmi P, Vairetti M. Changes in Biliary Levels of Arginine and its Methylated Derivatives after Hepatic Ischaemia/Reperfusion. Basic Clin Pharmacol Toxicol. 2016 Jul;119(1):101-9
• Di Pasqua LG, Berardo C, Rizzo V, Richelmi P, Croce AC, Vairetti M, Ferrigno A. MCD diet-induced steatohepatitis is associated with alterations in asymmetric dimethylarginine (ADMA) and its transporters. Mol Cell Biochem. 2016 Aug;419(1-2):147-55.
• Ferrigno A1, Rizzo V, Bianchi A, Di Pasqua LG, Berardo C, Richelmi P, Vairetti M. Changes in ADMA/DDAH pathway after hepatic ischemia/reperfusion injury in rats: the role of bile. Biomed Res Int., Epub 2014.

Links:
Scopus author’s page:
https://www.scopus.com/authid/detail.uri?authorId=6701488258
Department author’s page:
http://medint.unipv.eu/site/home/persone/docenti-e-ricercatori/scheda220001992.html