Role of de novo lipogenesis in insulin resistance in first-episode psychosis and therapeutic options.

ABSTRACT

Insulin resistance may precede the onset of psychosis in schizophrenia; however, the underlying mechanism remains unclear. While certain degree of inflammation is required for triggering insulin resistance, fatty acid accumulation is a crucial step in inflammation. And while all fatty acids can induce insulin resistance, effect of saturated fatty acids (SFAs) could be detrimental due to increase in oxidative stress and development of various inflammatory cues. Intriguingly, evidence suggest that while polyunsaturated fatty acids are reduced, SAFs are increased in the membrane phospholipids from patients with first-episode psychosis. This could be a result of enhanced de novo lipogenesis (DNL) because; antipsychotic treatment further deteriorates insulin resistance, increases DNL and SAF levels as evident by increase in obesity. Therefore, therapies targeting DNL or inflammation may reduce insulin resistance in schizophrenia. In this context, adjunctive treatment with certain anti-inflammatory agents, which seem to reduce DNL/SFAs levels, has shown significant improvement in cognitive and psychotic symptoms; however, its effect on insulin resistance in schizophrenia remain to be documented. In this regard, further large-scale clinical trials are warranted.