Antipsychotics-induced metabolic alterations: focus on adipose tissue and molecular mechanisms

Abstract

The use of antipsychotic drugs for the treatment of mood disorders and psychosis has increased dramatically over the last decade. Despite its consumption being associated with beneficial neuropsychiatric effects in patients, atypical antipsychotics (which are the most frequently prescribed antipsychotics) use is accompanied by some secondary adverse metabolic effects such as weight gain, dyslipidemia and glucose intolerance. The molecular mechanisms underlying these adverse effects are not fully understood but have been suggested to involve a dysregulation of adipose tissue homeostasis. As such, the aim of this paper is to review and discuss the role of adipose tissue in the development of secondary adverse metabolic effects induced by atypical antipsychotics. Data analyzed in this article suggest that atypical antipsychotics may increase adipose tissue (particularly visceral adipose tissue) lipogenesis, differentiation/hyperplasia, pro-inflammatory mediator secretion and insulin resistance and decrease adipose tissue lipolysis. Consequently, patients receiving antipsychotic medication could be at risk of developing obesity, type 2 diabetes and cardiovascular disease. A better knowledge of the impact of these drugs on adipose tissue homeostasis may unveil strategies to develop novel antipsychotic drugs with less adverse metabolic effects and to develop adjuvant therapies (e.g. behavioral and nutritional therapies) to neuropsychiatric patients receiving antipsychotic medication.

Keywords: Adipose tissue; Antipsychotics; Dyslipidemia; Glucose intolerance; Weight gain.