Caveolar Kv1.3 Targeting Participates in the Adipocyte Physiology

Abstract

The voltage-gated potassium channel Kv1.3 contributes to peripheral insulin sensitivity. KO mice for Kv1.3 are resistant to diet-induced weight gain. Therefore, this protein is being considered as a pharmacological target for obesity and associated type II diabetes. However, the expression of Kv1.3 in adipocytes generates controversy. Here, we found that Kv1.3 is present in white adipose tissue from humans and rodents. In addition, Kv1.1, Kv1.2, Kv1.4 and especially Kv1.5, from the same Shaker family are also present. Although elevated insulin levels and adipogenesis remodeled the Kv phenotype, which could trigger to numerous hybrid complexes, Kv1.3 noticeably participated in the insulin-dependent regulation of glucose transport in differentiated adipocytes. Adipogenesis increased the expression of Kv1.3 into caveolae by molecular interactions with caveolin 1. In a caveolin 1-deficient 3T3-L1 adipocyte cell line, we verified that the localization of Kv1.3 in caveolar lipid raft structures is necessary for proper insulin signaling. Insulin-dependent phosphorylation of the Kv1.3 occurs at the beginning of insulin-mediated signaling. However, when Kv1.3 localized out of these lipid microdomains, reduced phosphorylation was demonstrated. Our data contribute to the knowledge of the putative role of Kv1.3 in adipocyte physiology. Supported by the Ministerio de Ciencia, Innovación y Universidades, Spain (BFU2014-54928-R and BFU2017-87104-R) and Fondo Europeo de Desarrollo Regional (FEDER).