Endocrine Abstracts

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 ...

Obesity is associated with increased and dysfunctional white adipose tissue (WAT). Pharmacological approaches of obesity are still far from obtaining a stable weight loss. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been proposed as anti-obesity drugs due to their effects on weight loss. Furthermore, dual agonists engaging both GLP-1 and glucagon are currently under investigation for their marked effects on weight loss, although their mechanisms of action is stil...

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors. About 30-40% of Pheo/PGLs are due to a germ-line mutation in one of the 13 main susceptibility genes which include the genes encoding the four subunits of the succinate dehydrogenase (SDH - mitochondrial complex II). In PHEO/PGL due to SDHB mutations up to 80% of affected patients develop metastatic disease and no successful cure is at present available. To obtain an experimental model resembli...

The metabolic interplay occurring between the tumor microenvironment and cancer cells may represent a potential target for novel anti-cancer approaches. Among stromal components, adipocytes and adipose precursors have been shown to actively participate in tumor progression in several solid malignancies. In adrenocortical carcinoma (ACC), a rare endocrine neoplasia with a poor prognosis, cancer cells often infiltrate the fat mass surrounding the adrenal organ, enabling a possib...

Paragangliomas (PGLs) are rare neuroendocrine tumors. About 30–40% of these tumors are mutated in different susceptibility genes, including those encoding the different subunits of the succinate dehydrogenase, a complex involved both in the tricarboxylic acid cycle and in the oxygen transport chain. The aim of this project was to investigate whether SDHB mutations may account for alterations in cell metabolism and functions. Since PGL cell lines are not available, we used...

The potential therapeutic applications of targeting brown adipose tissue open new clinical avenues in fighting against metabolic pathologies. However, due to the limited brown depots in adult humans, dramatically reduced after birth, solid cell models to study human brown adipogenesis and its pathophysiological regulation are urgently needed.In our study, we characterized a novel human model of brown adipose stem cells, hfB-ASC, derived from fetal inters...

The recent discovery of the presence of brown adipose tissue (BAT) also in human adults is pivotal for development of anti-obesity therapies. This type of fat, in fact, mainly consists of brite cells (brown adipocytes appearing for a browning process in white fat) which are involved in adiposity control. The origin of brite cells in adult white adipose tissue (WAT) is still unclear as human cell models are lacking.Our study demonstrated the presence of B...

White adipose tissue acts as an endocrine organ that secretes a variety of adipokines and coordinates a number of biological processes such as energy homeostasis, neuroendocrine and immune functions. Recent studies demonstrated that abundant adipose tissue depots (particularly visceral adipose tissue), by producing inflammatory cytokines, contribute to chronic low-grade inflammation processes which may underlie the pathogenesis of metabolic disorders such as obesity, atheroscl...