Losartan is a well-known anti-hypertensive drug acting as a selective angiotensin II type 1 (AT1) receptor antagonist. In the present study, we investigated the effects of losartan on adipocyte browning, in association with apelin-APJ pathway. Losartan induced the expression of browning markers including uncoupling protein-1(UCP-1) in fully differentiated adipocytes, which was accompanied by reduced lipid droplets and increased mitochondrial biogenesis. In parallel, the expression of apelin and APJ was increased by losartan, concomitantly with increased phosphorylations of Akt and AMPK. On the other hand, knockdown of apelin or APJ expression by siRNA attenuated losartan-induced browning, suggesting that losartan-induced browning is mediated by the activation of apelin-APJ pathway. In vivo involvement of apelin in the losartan-induced browning was confirmed using C57BL/6J mice. In summary, these data suggest that losartan induces browning of white adipocytes via induction of apelin-APJ expression, which may imply its new application as an anti-obesity drug.

To: 要旨(抄録)