Serotonin 5‐HT2A receptor activity mediates adipocyte differentiation

Abstract

Serotonin 5‐HT2 receptors are expressed in variety of tissues and play important roles in many processes. The 5‐HT2A receptor is primary known for its role in CNS function. This receptor is, however, expressed in many peripheral tissues where its role remains largely unknown. Here, we present data demonstrating that blockade of 5‐HT2A activity inhibits adipocyte differentiation. This is a process in which pre‐adipocyte fibroblast accumulate lipids and fatty acids and become mature adipocyte. During the initiation of adipocyte differeantiation, transcription factors like CEBP‐b; are increased, which elevates levels of PPAR‐r, facilitating differentiation. Ketanserin, a 5‐HT2A/2C receptor antagonist inhibits both mouse and human adipocyte differeantiation in a dose dependent manner. The IC50 of ketanserin in a primary human preadipocyte model is 78 nM. Using selective 5‐HT2A/2B/2C receptor antagonist, we discovered that blockade of 5‐HT2A or 5‐HT2B receptors but not 5‐HT2C receptors was effective to prevent adipocyte differentiation. Time course analysis indicates that 5‐HT2A receptor activity is necessary very early in the induction phase to facilitate differentiation. Together, these data indicate that 5‐HT2A receptors play an important role in adipocyte differentiation. Studies probing the effects of 5‐HT2A receptor blockade on molecular markers of adipocyte differenetiation are ongoing.