AUTHOR=Schiavone Stefania , Camerino Giulia M. , Mhillaj Emanuela , Zotti Margherita , Colaianna Marilena , De Giorgi Angelo , Trotta Antonello , Cantatore Francesco P. , Conte Elena , Bove Maria , Tucci Paolo , Morgese Maria G. , Trabace Luigia 

TITLE=Visceral Fat Dysfunctions in the Rat Social Isolation Model of Psychosis

JOURNAL=Frontiers in Pharmacology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00787

DOI=10.3389/fphar.2017.00787

ISSN=1663-9812

ABSTRACT=<p>Medication with neuroleptics has been associated with adipose tissue dysfunctions and, in particular, with increased visceral fat amount. However, several studies suggested that antipsychotic treatment might not be the main responsible of fat mass accumulation, as this has been also described in not treated psychotic patients. One of the most used “drug-free” rodent models of psychosis is the social isolation rearing of young adult rats, which provides a non-pharmacologic method of inducing long-term alterations reminiscent of symptoms seen in psychotic patients. Recent data highlighted a crucial role of redox imbalance in adipose tissue dysfunctions, in terms of decreased antioxidant defense and increased reactive oxygen species (ROS). Here, we investigated possible oxidative stress-related biomolecular alterations associated with visceral fat increase in 7 week isolated rats. To this purpose, we quantified total and visceral fat amount by using dual-energy X-ray (DEXA) absorptiometry. On visceral fat, we analyzed the expression of specific ROS-producer genes (<italic>Nox1, Nox4, Hmox-1</italic>), antioxidant enzymes (<italic>Prdx1</italic> and <italic>Ucp-1</italic>) and oxidative stress-induced damage markers (<italic>Cidea, Slc2a4</italic>, and <italic>Acacb</italic>). The impact of oxidative stress on beta3-adrenergic receptors (<italic>Adrb3</italic>), at both mRNA and protein level, was also assessed. We found that 7 weeks of social isolation induced an increase in total and visceral fat, associated with a decrease in <italic>Prdx1</italic> (mRNA and protein) as well as <italic>Ucp-1</italic> mRNA levels and an enhanced expression of <italic>Nox1</italic> (mRNA and protein) and <italic>Hmox-1</italic> mRNA. No differences were detected in <italic>Nox4</italic> mRNA levels between grouped and isolated animals. Elevations in <italic>Cidea</italic>, <italic>Slc2a4</italic>, and <italic>Acacb</italic> expression in visceral fat of isolated animals accounted for oxidative stress-related damage in this tissue, further associated with a significant increase in <italic>Adrb3</italic> mRNA and protein. Our results provide a novel understanding of the pathological link existing among psychosocial stress-induced psychosis, adipose tissue dysfunctions and redox imbalance, opening new therapeutic perspectives for the treatment of alterations in peripheral tissues associated with this mental disorder.</p>