Aurora Daniele

A) ROLE OF ADIPONECTIN IN THE PREVENTION OF OBESITY AND METABOLIC SINDROME

Adiponectin is a protein hormone produced by adipose tissue and secreted in serum; it is involved in regulating glucose and lipid metabolism, modulating the action of insulin, possessing anti-inflammatory properties exerting protective effects on the development of associated pathologies obesity. The expression of adiponectin in the serum of healthy subjects is about 5-30 mg/ml, representing 0.01% of the total proteins. In patients with metabolic diseases such as obesity related diseases, adiponectin levels considerably decrease. Adiponectin circulates in the serum as oligomers of different weight. This adipokine is processed into at least three oligomeric complexes, trimers (low molecular weight: LMW), hexamers (medium molecular weight MMW) and high molecular weight forms (HMW). There is growing interest in the role of these complexes in metabolism and disease as several lines of evidence suggest that oligomeric state affects the biological activity of adiponectin. Indeed, HMW represent the oligomers with the highest biological activity. Adiponectin plays its beneficial functions via three receptors, AdipoR1 and AdipoR2 that belong to the family of seven transmembrane receptors and are widely expressed in various tissues and organs and T-cadherin, mainly expressed on endothelial cells. The adiponectin gene, ApM1, maps on chromosome 3 and consists of 3 exons. In obesity and related diseases, serum levels of adiponectin are reduced and its mechanism of action is altered. Our research team is concerned characterizing: a) the ApM1 gene in a population of severely obese subjects; b) adiponectin serum levels in adult and pediatric patients affected by obesity and/or related metabolic pathologies c) the molecular mechanisms of adiponectin action in obesity d) adiponectin receptors expression in adipose tissue from patients affected by obesity and subjected to bariatric surgery.

B) ROLE OF ADIPONECTIN IN LUNG AND COLON CANCER

Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and risk of several cancers. However, data on serum adiponectin expression in cancer patients are still inconclusive, decreased or unmodified levels of adiponectin have been reported. Also in vitro studies reported contrasting results; some authors found that adiponectin exerts pro-proliferative effects while others demonstrated an inhibitory role for adiponectin in several cellular models of carcinoma. Our studies explore the possibility to use adiponectin as a diagnostic and prognostic marker in lung and colon cancer. In addition, we analyze adiponectin molecular effects in terms of proliferation, apoptosis, inflammation and oxidative stress. Our data will help to understand whether adiponectin and its receptors could represent a useful tool for the follow-up of patients with lung and colon cancer strengthening a direct role of the adiponectin system in carcinogenesis.

C) ROLE OF ADIPONECTIN IN IMMUNE SYSTEM DISORDERS

Adipose tissue is an active organ involved not only in energy homeostasis but also in inflammatory- and immune-related functions by producing bioactive mediators called adipokines. Amongst adipokines, adiponectin has anti-inflammatory and immune-suppressive effects inhibiting the phagocytic activity of macrophages, decreasing tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 production. Common variable immunodeficiency (CVID) is a severe immunodeficiency disorder that impairs the immune system. People with CVID are highly susceptible to infection from foreign invaders such as bacteria, or more rarely, viruses and often develop recurrent infections and cancer. Multiple sclerosis is a neurological condition that affects central nervous system. It is a demyelinating disease in which nerve cells and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a range of signs and symptoms, including physical, mental. Our research activities focus on the evaluation of total Adiponectin and HMW oligomers in CVID and multiple sclerosis patients before and after immunoglobulin infusion (routine treatment for CVID patients). In addition, we evaluate the molecular mechanisms at the basis of Adiponectin  modulation in CVID by evaluating the peripheral blood leucocytes cells profiling as well as the expression of AdipoR1, AdipoR2 and T-cadherin on peripheral blood leucocytes from CVID patients before and after IG replacement therapy and in comparison, to healthy controls. In addition, since B cells are influenced by different cytokines, we will test IL-2, IL-6, IL-10, TNFa, IFNg concentrations in serum of patients and controls by Elisa test. Our study, clarifying the molecular mechanisms of adiponectin regulation in immune responses, would allow the use of this adipokine as a biomarker in the therapeutic management of immune disorder’s patients.

D) MOLECULAR ANALYSIS OF PKD1 AND2 IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited cause of kidney failure, is caused by mutations in either PKD1 (85%) or PKD2 (15%). The PKD2 protein, polycystin-2 (PC2 or TRPP2), is a member of the transient receptor potential (TRP) superfamily and functions as a nonselective calcium channel. PC2 has been found to form oligomers in native tissues it may form functional homo- or heterotetramers with other TRP subunits. ADPKD is a genetic disorder characterized by numerous cysts in the kidneys. ADPKD is caused by mutations in the PKD1 and PKD2 genes, transient receptor potential cation channels. Our activity is focused on the development of a rapid but reliable molecular analysis of those two genes involved in ADPKD. We are exploring a next generation sequencing approach to perform the molecular analysis of PKD1 and PKD2 genes to ameliorate and personalize the therapeutic protocol.