Int J Oral Biol.  2018 Mar;43(1):23-27. 10.11620/IJOB.2018.43.1.023.

Channel Function of TRPML1 Prompts Lipolysis in Mature Adipocytes

• Kim MS
• Kim MS

• KMID: 2437481
• DOI: http://doi.org/10.11620/IJOB.2018.43.1.023

Abstract

Increased intracellular levels of Ca²âº are generally thought to negatively regulate lipolysis in mature adipocytes, whereas store-operated Ca²âº entry was recently reported to facilitate lipolysis and attenuate lipotoxicity by inducing lipophagy. Transient receptor potential mucolipin1 (TRPML1), a Ca²âº-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.

Keyword

Transient receptor potential mucolipin1; lipolysis; ML-SA1; adipocyte

MeSH Terms

Adipocytes*
Glycerol
Homeostasis
Isoproterenol
Lipid Metabolism
Lipolysis*
Membranes
Obesity
Glycerol
Isoproterenol