Abstract
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 (Nox1, Nox4, Hmox-1), antioxidant enzymes (Prdx1 and Ucp-1) and oxidative stress-induced damage markers (Cidea, Slc2a4, and Acacb). The impact of oxidative stress on beta3-adrenergic receptors (Adrb3), 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 Prdx1 (mRNA and protein) as well as Ucp-1 mRNA levels and an enhanced expression of Nox1 (mRNA and protein) and Hmox-1 mRNA. No differences were detected in Nox4 mRNA levels between grouped and isolated animals. Elevations in Cidea, Slc2a4, and Acacb expression in visceral fat of isolated animals accounted for oxidative stress-related damage in this tissue, further associated with a significant increase in Adrb3 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.
Highlights
Psychosis and Adipose Tissue DysfunctionsAmong psychiatric diseases, psychosis represents one of the most impacting cause of disability (Vigo et al, 2016), with a consequent increased international trend in antipsychotic prescription (Verdoux et al, 2010)
One of the most used drug-free rodent model of psychosis is the social isolation rearing of young adult rats (Weiss and Feldon, 2001; Leng et al, 2004), which provides a non-pharmacologic method of inducing long-term alterations reminiscent of several symptoms seen in psychotic patients (King et al, 2009), including hyperreactivity to novel environments and cognitive impairment (Geyer and Ellenbroek, 2003; Lapiz et al, 2003)
In order to evaluate if social isolation rearing might affect adipose tissue amount, we evaluated total and visceral fat mass by dual-energy X-ray (DEXA) in rats reared in group and in animals exposed to a 7-week period of social isolation
Summary
Psychosis and Adipose Tissue DysfunctionsAmong psychiatric diseases, psychosis represents one of the most impacting cause of disability (Vigo et al, 2016), with a consequent increased international trend in antipsychotic prescription (Verdoux et al, 2010). The underlying pathological mechanisms are poorly understood, social deprivation of rat pups during a critical period, such as from weaning through adulthood, appears as a strong psychosocial stress, which is thought to contribute to the etiology of mental disorders, such as psychiatric conditions in humans (Schiavone et al, 2013). Together with these symptoms, accumulating evidence suggests that deprivation of social interactions is significantly associated with several metabolic disturbances, including hypertension, cardiovascular dysfunctions, and adipose tissue dysfunctions (Bartolomucci et al, 2009)
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