Role of Endothelin-1 in the Brown Adipose Tissue

Abstract

ET-1 was shown to inhibit adipogenesis in murine mesenchymal stem cells derived from new-born brown adipose tissue in vitro and antagonism of Endothelin-1 (ET-1) signaling at the respective level of the Endothelin-1 receptor A (ETA) enhanced differentiation of brown adipocytes in vitro, which was quantified by increased brown adipocyte-marker expression. Based on in vitro data, in vivo studies were conducted in order to put the therapeutic strategy of ETA-antagonism to the test. In the conducted studies two approaches were taken to realize whether or not beneficial effects arise from ETA-antagonism: First, ETA was antagonized pharmacologically with BQ-123. Secondly, ETA was genetically deleted (Ednra-ATKO) in the adipose tissue using the cre-lox system. Both approaches were tested in a setting of diet-induced obesity and chronic cold-exposure. In the settings of diet-induced obesity, neither pharmacological inhibition nor genetic ablation proved to be clearly beneficial. The pharmacological antagonism upon BQ-123-treatment induced a minor but significant upregulation of the functional marker Ucp1 in brown adipose tissue after chronic cold-exposure.