Prof. Stefano Fiorucci invito dall' Accademia Russa delle Scienze conferenza a San Pietroburgo su recettori nucleari e recettori per acid biliari utilizzati nel trattamento del diabete ed obesità e loro applicazione clinica

1. RUSSIAN ACADEMY OF SCIENCES
Institute of Macromolecular Compounds
St. Petersburg
PROF. STEFANO FIORUCCI
SECTION OF GASTROENTEROLOGY
DEPARTMENT OF SURGERY AND BIOMEDICAL SCIENCES,
UNIVERSITY OF PERUGIA MEDICAL SCHOOL
BILE ACID ACTIVATED RECEPTORS: TALE OF A MULTITASKING
FAMILY
Nuclear receptors (NRs) are a large family of ligand-activated transcription
factors (Human NR superfamily include 48 members) which control numerous
metabolic pathways and processes in various organs, ranging from
proliferation to apoptosis, differentiation and energy homeostasis. Nuclear
receptors as valuable potential targets for the development of therapeutic
agents against a number of pathological conditions and diseases. Bile acids,
are the end-products of cholestrol metabolism synthesized in the liver and
secreted in the gastrointestinal tract where they undergoes a transformation
by the intestinal microbiota. In addition to their role in regulating lipid and
cholesterol absorption in the small intestinal, bile acids area signaling
molecules acting on wide range of receptors collectively known as Bile acid
activated receptors (BARs). This family includes NR such as The farnesoid
X receptor (FXR), the Vitamin D receptor (VDR), the pregnane-x-receptor
(PXR) among others and G-protein coupled receptors such as GPBAR1
(TGR5). FXR is a bile sensor that acts in coordination with other nuclear
receptors to regulate essential steps in bile acid uptake, metabolism and
excretion. FXR shares the general architecture of other NR receptors acting
as an heterodimer with RXR (retinoid-x-receptor). In addition, FXR is
involved in lipid and glucose homeostasis. FXR ligands endowed with
agonistic activity are under development for the treatment of metabolic
disorders linked to insulin resistance. GPBAR1 is a receptor regulating
energy expenditure and has relevance in the treatment of insulin resistance
and diabetes along with inflammation and immune dysfunction.
Objectives
- To describe cholesterol/bile acid metabolism and receptors
- Biology of BAR
- Medicinal chemistry of FXR and GPBAR1

2. -Potential clinical application