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.

Introduction
 Materials and Methods
  Materials and cell culture
  In vitro adipogenesis assay
  Western blotting
  Glycerol release assay
  Statistical analysis
 Results
  Treatment of ML-SA1 without activation of β -adrenergic receptor upregulates extracellularglycerol release
  Deletion of TRPML1 in mature adipocytes results inreduction of LC3 cleavage
 Discussion
 Acknowledgements
 References

• Mi Seong Kim(Center for Metabolic Function Regulation, School of Medicine, No. 460, Wonkwang University)
• Min Seuk Kim(Department of Oral Physiology, and Institute of Biomaterial-Implant, School of Dentistry, Wonkwang University) Correspondence to