Endocrine Abstracts

The nuclear Farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5) are bile acids receptors that play a key role in energy metabolism. In an animal model of non-genomic metabolic syndrome (MetS), obtained with a high fat diet (HFD), treatment with the dual FXR/TGR5 agonist INT767 reduced visceral adipose tissue (VAT) accumulation, insulin resistance, hypercholesterolemia and nonalcoholic steatohepatitis (NASH). In liver, INT767 reduced the high macrop...

Increased RhoA/Rho-kinase (ROK) signalling is known to impair erectile function. Spontaneously hypertensive rats (SHR) over-express penile RhoA and show an impaired erectile response. We tested treatments known to inhibit RhoA activation, on erectile function and sildenafil responsiveness in SHR. SHR have been treated for two weeks with atorvastatin (5 and 30 mg/Kg/day), or with elocalcitol (30 μg/Kg/day), a vitamin D receptor (VDR) agonist. The normotensive Wistar Kyoto ...

Expanding brown adipose tissue is a potential therapeutic strategy to counteract insulin resistance and metabolic syndrome (MetS). Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) activation enhances insulin sensitivity, suggesting the capacity of FXR/TGR5 agonists to promote brown differentiation in adipose tissue. Treatment with increasing doses of the dual FXR/TGR5 agonist INT-767 (3, 10, 30 mg/Kg bw, daily for 5 days a week, by oral gavage, for 12 ...

Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) are interesting pharmacological targets for the treatment of liver and metabolic diseases. FXR-deficient mice on a high-fat diet (HFD) exhibit massive hepatic steatosis, necro-inflammation and fibrogenesis. Moreover, pharmacological activation of TGR5 in mice promotes protective mechanisms in biliary epithelial cells and inhibits hepatic and systemic inflammation. Thus, we hypothesized that a FXR/TGR5 du...

A pathogenic link between erectile dysfunction (ED) and metabolic syndrome (MetS) is now well established. Nonalcoholic steatohepatitis (NASH), the hepatic hallmark of MetS, is regarded as an active player in the pathogenesis of MetS-associated cardiovascular disease (CVD). This study was aimed at evaluating the relationship between MetS-induced NASH and penile dysfunction. We used a non-genomic, high fat diet (HFD)-induced, rabbit model of MetS, and treated HFD rabbits with t...

Liver and visceral ectopic fatty tissue disposition is a major metabolic derangement leading to type 2 diabetes, hypertension, dyslipidaemia, recapitulated in the metabolic syndrome (MetS). We have demonstrated that the selective FXR agonist obeticholic acid (OCA, INT-747) ameliorates the metabolic profile and reduces visceral adipose tissue (VAT) in a high-fat diet (HFD)-induced rabbit model of MetS. We now report the effects of OCA treatment in HFD (0.5% cholesterol and 4% p...

Human bladder contraction mainly depends on Ca2+ influx, via L-type voltage-gated Ca2+ channels, and on RhoA/Rho-kinase contractile signalling, a pathway up-regulated in overactive bladder (OAB) syndrome. Elocalcitol (Elo) is a vitamin D receptor agonist inhibiting RhoA/Rho-kinase signalling in rat and human bladder, shown to ameliorate OAB symptoms in a clinical study. Since in normal bladder from Sprague–Dawley (SD) rats Elo treatment delayed the c...