Cetrimonium bromide promotes lipid clearance via TFEB-mediated autophagy-lysosome activation in hepatic cells.

Cetrimonium bromide promotes lipid clearance via TFEB-mediated autophagy-lysosome activation in hepatic cells. Biochem Cell Biol. 2021 Feb 09;: Authors: Liu Z, Wang X, Shi Z, Xu J, Lin J, Li D, Zhang X, Li Y, Zhao Q, Tao L, Diao A Abstract Autophagy plays a key role in the metabolism of macromolecules by the lysosomal degradative machinery. The transcription factor EB (TFEB) regulates autophagosome biogenesis and lysosome function, and promoting TFEB activity has emerged as a potential strategy for the treatment of metabolic disorders. Here, we describe that cetrimonium bromide (CTAB), a quaternary ammonium compound, promotes autophagy and lysosomal biogenesis by inducing the nuclear translocation of TFEB in hepatic cells. shRNA-mediated TFEB knockdown inhibits CTAB-induced autophagy and lysosomal biogenesis. Mechanistically, CTAB treatment inhibits the Akt-mTORC1 signaling pathway. Moreover, CTAB treatment markedly promotes lipid metabolism in both palmitate and oleate-treated HepG2 cells, and this promotion was attenuated by the depletion of TFEB. Altogether, our results indicate that CTAB activates the autophagy-lysosome pathway by inducing the nuclear translocation of TFEB via the inhibition of mTORC1 signaling. These results deepen our understanding of TFEB function and provide new insights into CTAB-mediated lipid metabolism. PMID: 33560918 [PubMed - as supplied by publisher]
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Biochem Cell Biol Source Type: research