MiR-143 targets SYK to regulate NEFA uptake and contribute to thermogenesis in male mice.

Abstract

Excessive energy intake is the main cause of obesity, and stimulation of brown adipose tissue (BAT) and white adipose tissue (WAT) thermogenesis has emerged as an attractive tool for anti-obesity. Although miR-143 has been reported to be associated with BAT thermogenesis, its role remains unclear. Here, we found that miR-143 was highest expression in adipose tissue, especially in BAT. During short-term cold exposure or CL316,243 injected, miR-143 was markedly down-regulated in BAT and subcutaneous WAT (scWAT). Moreover, knockout of miR-143 (KO) increases the body temperature of mice upon cold exposure, which may be due to the increased thermogenesis of BAT and scWAT. More importantly, supplement of miR-143 in BAT of KO mice can inhibit the increase of body temperature in KO mice. Mechanistically, spleen tyrosine kinase (SYK) was revealed for the first time as a new target of miR-143, and deletion of miR-143 facilitates fatty acid uptake in BAT. In addition, we found that brown adipocytes can promote fat mobilization of white adipocytes, and miR-143 may participate in this process. Meanwhile, we demonstrate that inactivation of AC9 in BAT inhibits thermogenesis through AC9-PKA-AMPK-CREB-UCP1 signaling pathway. Overall, our results reveal a novel function of miR-143 on thermogenesis, and a new functional link of the BAT and WAT.