Increased intracellular levels of Ca2+ are generally thought to negatively regulate lipolysis in mature adipocytes, whereas store-operated Ca2+ entry was recently reported to facilitate lipolysis and attenuate lipotoxicity by inducing lipophagy. Transient receptor potential mucolipin1 (TRPML1), a Ca2+-permeable non-selective cation channel, is mainly expressed on the lysosomal membrane and plays key roles in lysosomal homeostasis and membrane trafficking. However, the roles of TRPML1 in lipolysis remains unclear. In this study, we examined whether the channel function of TRPML1 induces lipolysis in mature adipocytes. We found that treatment of mature adipocytes with ML-SA1, a specific agonist of TRPML1, solely upregulated extracellular glycerol release, but not to the same extent as isoproterenol. In addition, knockdown of TRPML1 in mature adipocytes significantly reduced autophagic flux, regardless of ML-SA1 treatment. Our findings demonstrate that the channel function of TRPML1 partially contributes to lipid metabolism and autophagic membrane trafficking, suggesting that TRPML1, particularly the channel function of TRPML1, is as therapeutic target molecule for treating obesity.

Slim813은 2-사이클로펜텐-1-온 옥심 유도체로서 다양한 염증성 자극원에 대한 TNF 생성을 억제하는 항 자극 및 UV에 의한 MMP1 억제를 통한 항 노화 효능을 갖는 물질이다. 본 연구를 통하여 이와 같은 효능 외에도 완전히 분화된 지방 세포에서 cAMP (cyclic adenosine monophosphate) 생성 촉진을 통한 HSL (hormone sensitive lipase) 활성을 증대시킴으로써 지방분해를 증가시킴을 확인하였다. 또한 Slim813을 사람의 팔과 허벅지 부위에 2주간 도포하였을 때 지방의 두께 감소를 유발하는 것으로 나타나 체내 피하 지방을 분해하는 효능을 갖는 것으로 사료된다.