Effect of Dibutyltin Dilaurate on Triglyceride Metabolism through the Inhibition of the mTOR Pathway in Human HL7702 Liver Cells

Abstract

Dibutyltin dilaurate (DBTD) has multiple applications in daily life. However, DBTD is easily deposited in the liver and affects liver functions. This study was designed to explore the effects of DBTD on triglyceride metabolism in human normal hepatocyte HL7702 cells. Our results showed that the intracellular fat contents were dose-dependently decreased by DBTD. The expression of lipolysis genes and proteins were elevated while the lipogenesis genes and proteins were diminished by DBTD. The phosphorylation levels of ribosomal S6 kinase 1 were reduced by both rapamycin and DBTD, indicating that the mTOR pathway was suppressed possibly. The decreased sterol regulatory element-binding protein 1C (SREBP1C) transcription levels, as well as the increased peroxisome proliferator-activated receptor alpha (PPARα) transcription levels, caused by rapamycin and DBTD corresponded to the inactive mTOR pathway. In conclusion, it was possible that DBTD reduced the intracellular triglyceride through depressing the mTOR pathway and affecting its downstream transcription factors.

Fatty-acid-derived ester-urethane macromonomers synthesized using bismuth and zinc catalysts

“…11 However, tin-based compounds and organotin compounds, such as DBTDL in particular, exhibit cytotoxicity, 12 are difficult to remove from polymers, and have adverse environmental effects. 13 Therefore, their usage in medical applications is limited 14 and there is growing interest in "greener" organotin-free reaction pathways. 15 Towards this aim, alternative catalytic systems are being explored that replace tin with other metals, such as zinc, titanium, zirconium, manganese, etc.…”

Schizandrin protects H9c2 cells against lipopolysaccharide‐induced injury by downregulating Smad3

“…A growing number of studies have suggested that traditional Chinese medicines exert beneficial effects via modulation of the transcription of related genes . To date, several genes have been reported to be the downstream effectors of schizandrin, including hefA and thymic stromal lymphopoietin .…”

PPAR-Mediated Toxicology and Applied Pharmacology

“…The decreased expression levels of cluster of differentiation 36 (CD36), fatty acid binding protein 4 (FABP4), enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), acetyl-CoA acyltransferase 1 (ACAA1), phosphoenolpyruvate carboxykinase (PEPCK), PPARα, and PPARγ in DBDCT-treated liver tissue were indicated by proteomics. Furthermore, the toxic effect was alleviated by PPARγ blocking agent T0070907 [42,43]. Additionally, organotins, the major components of agricultural fungicides and pesticides, were documented to exert similar functions as PPARγ and PPARβ ligands, which promote weight gain and increase fat storage by target gene induction in liver [44].…”