Search

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.

Matteo Briguglio,1,* Jacopo Antonino Vitale,1 Roberta Galentino,2 Giuseppe Banfi,1,3 Carlotta Zanaboni Dina,4 Alberto Bona,5 Giancarlo Panzica,6 Mauro Porta,2,* Bernardo Dell’Osso,7–9,* Ira David Glick9,* 1IRCCS Orthopedic Institute Galeazzi, Scientific Direction, Milan, Italy; 2IRCCS Orthopedic Institute Galeazzi, Tourette’s Syndrome and Movement Disorders Centre, Milan, Italy; 3Department of Medicine and Surgery, Vita-Salute San Raffaele University, Milan, Italy; 4TICEA Center, Scientific Direction, Milan, Italy; 5Neurosurgery Department, ICCS Istituto Clinico Città Studi, Milan, Italy; 6Department of Neuroscience, Rita Levi Montalcini, University of Turin, Turin, Italy; 7University of Milan, Department of Clinical and Biomedical Sciences Luigi Sacco, ASST Fatebenefratelli-Sacco, Ospedale Sacco Polo Universitario, Milan, Italy; 8“Aldo Ravelli” Center for Neurotechnology and Brain Therapeutic, University of Milan, Milan, Italy; 9Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA*These authors contributed equally to this workCorrespondence: Matteo BriguglioIRCCS Orthopedic Institute Galeazzi, Scientific Direction, Via Riccardo Galeazzi, 4, Milan 20161, MI, ItalyTel +39 338 6087042Email matteo.briguglio@grupposandonato.itAbstract: Neuropsychiatric disorders stem from gene-environment interaction and their development can be, at least in some cases, prevented by the adoption of healthy and protective lifestyles. Once full blown, neuropsychiatric disorders are prevalent conditions that patients live with a great burden of disability. Indeed, the determinants that increase the affliction of neuropsychiatric disorders are various, with unhealthy lifestyles providing a significant contribution in the interplay between genetic, epigenetic, and environmental factors that ultimately represent the pathophysiological basis of these impairing conditions. On one hand, the adoption of Healthy Eating education, Physical Activity programs, and Sleep hygiene promotion (HEPAS) has the potential to become one of the most suitable interventions to reduce the risk to develop neuropsychiatric disorders, while, on the other hand, its integration with pharmacological and psychological therapies seems to be essential in the overall management of neuropsychiatric disorders in order to reduce the disability and improve the quality of life of affected patients. We present an overview of the current evidence in relation to HEPAS components in the prevention and management of neuropsychiatric disorders and provide suggestions for clinical practice.Keywords: neuropsychiatry, diet, motor activity, sleep, quality of health care

Background and purpose: Fingolimod is a drug approved for treatment of relapsing‐remitting multiple sclerosis (RRMS) that exerts its effects via sequestering lymphocytes within the lymph nodes. The drug, acting on the sphingosine‐1‐phosphate pathway, is involved in a plethora of processes and, to date, its mechanism of action is not completely understood. Recently, it has been demonstrated that Fingolimod increases the expression of transcription factor NR4A2 in murine brain. NR4A2 belongs to nuclear receptor family 4, group A (NR4A) along with NR4A1 and NR4A3. The role of NR4A2 in the pathogenesis of multiple sclerosis is already known and supported by its down‐regulation observed in blood obtained from patients with RRMS compared with healthy controls (HCs). It is notable that NR4A2 impairment is reversed in patients with RRMS during pregnancy, which represents a transitory state of immune tolerance, associated with reduced disease activity. An inverse correlation between NR4A2 gene expression levels and clinical parameters indicates that more aggressive forms of the disease are characterized by lower levels of NR4A2. Methods: Gene expression levels of NR4A in blood obtained from HCs, treatment‐naive (T0) and Fingolimod‐treated patients with RRMS were evaluated to determine their contribution to drug response. Results: Gene expression levels of NR4A were down‐regulated in T0 patients compared with HCs. Patients treated with Fingolimod for >2 years were characterized by higher levels of NR4A2 compared with the T0 group, approaching those of HCs. NR4A1 and NR4A3 levels were not altered. Conclusions: Involvement of the NR4A family in the pathogenesis of multiple sclerosis and a role of Fingolimod in the recovery from NR4A2 deficit can be hypothesized based on our data. [ABSTRACT FROM AUTHOR]