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...

Background: Metabolic syndrome (MetS) is a clustering of metabolic and cardiovascular risk factors, with insulin resistance being one of the main components. In male, MetS is also associated to hypogonadotropic hypogonadism. Lifestyle modifications (e.g. physical activity) could prevent or considerably reduce MetS progression, however the ability to perform physical activity is often impaired in MetS subjects.Aim: Considering the known trophic role of T ...

Pathologies of the female reproductive system, characterized by chronic pain, are frequent and it has been hypothesized that inflammation may play an essential role in their pathogenesis. It is known that androgens, including dihydrotestosterone (DHT), have shown immunomodulatory effects in experimental models of chronic inflammation. The aim of this study was to evaluate the immunomodulatory effects of DHT in smooth muscle cells (rSMCs) isolated from vagina of intact Sprague-...

Metabolic syndrome (MetS) is a clustering of cardio-metabolic risk factors (hyperglycemia, hypertension, dyslipidemia, visceral fat accumulation) that is also associated with hypogonadism and erectile dysfunction (ED). The study was aimed at clarifying the relationships among MetS, hypogonadism, and ED, we developed an animal model of MetS.Methods: Male rabbits fed a high-fat diet (HFD), with or without testosterone (T) supplementation, were compared wit...

Metabolic syndrome (MetS) clusters cardiovascular and metabolic risk factors, along with hypogonadism (HG) and erectile dysfunction (ED). Lifestyle modifications, including physical exercise (PhyEx), are well-known treatments for this condition. We previously established a non-genomic, high-fat diet (HFD)-induced rabbit model of MetS that recapitulates the human phenotype, including HG and ED. We now report studies on the effect of PhyEx on hypothalamus-pituitary-testis (HPT) ...

Inflammation is hypothesized to play an important role in several diseases associated to the female genital tract and dihydrotestosterone (DHT) has shown immunomodulatory protective effects in experimental models of chronic inflammation. In the present study we aimed to evaluate the potential anti-inflammatory effects of DHT in a model of smooth muscle cells (hSMCs) isolated from human vagina biopsies and their potential role as APCs (Antigen Presenting Cells), crucial for the...

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...

The metabolic syndrome (MetS) is a clustering of metabolic and cardiovascular risk factors, having in insulin resistance the key element. In males, MetS is also associated to hypogonadism. We recently found that high fat diet (HFD)-induced MetS rabbits also developed hypogonadotropic hypogonadism, showing a reduced immunopositivity for gonadotropin relasing hormone (GnRH) in the hypothalamus. In this study, we investigated the pathogenetic link between Mets components and the ...

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...