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Serotonin 5-HT 2  receptors are expressed in many tissues and play important roles in biological processes. Although the 5-HT 2A  receptor is primarily known for its role in central nervous system, it is also expressed in peripheral tissues. We have found that 5-HT 2A  receptor antagonists inhibit human subcutaneous primary adipocyte differentiation. We also show that siRNA knockdown of the 5-HT 2A  receptor blocks differentiation. Using gene expression analysis in combination with receptor antagonists we found that activity of 5-HT 2A  receptors is necessary very early in the differentiation process to mediate expression of adipogenic genes, including  peroxisome proliferator-activated receptor gamma (ppar-γ), adipocyte protein 2 (aP2) ,  adiponectin , and  serine/threonine-protein kinase 1 (sgk1) . We show here for the first time that 5-HT 2A  receptor activity is necessary for differentiation of human primary subcutaneous preadipocytes to adipocytes, and that 5-HT 2A  receptor activity mediates key genes related to adipogenesis during this process. Importantly, this work contributes to a greater understanding of the adipocyte differentiation process, as well as to the role of 5-HT 2A  receptors in peripheral tissues, and may be relevant to the development of novel therapeutic strategies targeting this receptor for the treatment of obesity related diseases.

Serotonin 5-HT2A receptor activity mediates adipocyte differentiation through control of adipogenic gene expression