Metabolic Signature of Antipsychotics used in the Treatment of Autism
Annual rept. 30 Sep 2013-29 Sep 2014
CINCINNATI UNIV OH
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Atypical antipsychotics AAP are prescribed to millions of patients with neuropsychiatric disorders. Although SGAs can ameliorate mental dysfunctions, they have serious metabolic side-effects such as weight gain, the metabolic syndrome, and increased risk of diabetes and cardiovascular disease. The current dogma is that metabolic side effects of AAP are attributed to their action on neuronal circuits the brain. However, we previously discovered expression of functional dopamine and serotonin receptors in human and rodent adipocytes and proposed that these receptors are targeted by AAP. In vivo studies with rats and in vitro studies with human adipocytes demonstrated multiple direct effects of AAP on adipose tissue. These include increased food intake, fat accumulation, enlargement of adipocytes, alterations in key metabolic genes, changes in the secretion of leptin and adiponectin and suppression of basal and isoproterenol-stimulated lipolysis. We conclude that AAPinduced metabolic dysregulation is caused, in part, by their direct action on adipose tissue, presumably via the local dopamine and serotonin receptor subtypes.
- Medicine and Medical Research