Kv1.3 in adipose tissue: characterization of adipocyte-specific KCNA3 knockout mouse model

The voltage-gated potassium channel Kv1.3 is widely expressed in both excitable and non-excitable cells and has been studied as a pharmacological target in cancer, auto-immune, and neurodegenerative disorders. More recently, Kv1.3 has been also recognized to play a role in metabolic homeostasis, acting both at central nervous system and peripheral tissues levels. Global Kv1.3 knockout mice exhibit resistance to diet-induced obesity, increased energy expenditure and enhanced insulin sensitivity. However, the specific cell types mediating these effects remain undefined. Adipose tissue is a very plastic organ whose functional state is closely linked to the development of obesity and metabolic disorders. This tissue expresses a wide range of ion channels which are fundamental for adipocytes physiology and tissue remodeling. This thesis aims to characterize a conditional knockout mouse model (Adipoq∆Kv1.3), in which the KCNA3 gene is selectively deleted in mature adipocytes, evaluating morphological and functional changes in adipose tissue.