sirolimus and palmitoleic-acid

Previous studies indicate that the transcription factor upstream stimulating factor 1 (USF1) is involved in the regulation of lipid and glucose metabolism. However, the role of USF1 in lipid-induced autophagy remains unknown. Interestingly, we found that USF1 overexpression suppresses autophagy-related gene expression in HepG2 cells. Further assays confirmed that USF1 could transcriptionally activate mTOR expression, thereby suppressing rapamycin-induced autophagy in HepG2 cells. Moreover, pharmacological activation of autophagy with rapamycin decreases the numbers and sizes of lipid droplets (LDs) in HepG2 cells exposed to an oleate/palmitate mixture. Of note, USF1 upregulation decreases colocalization of LDs and autophagosomes. In conclusion, our data provide evidence that USF1 contributes to abnormal lipid accumulation in the liver by suppressing autophagy via regulation of mTOR transcription.

Topics: Animals; Autophagy; Autophagy-Related Proteins; Diet, High-Fat; Disease Models, Animal; Fatty Acids, Monounsaturated; Gene Expression Regulation; Hep G2 Cells; Humans; Lipid Droplets; Liver; Mice; Non-alcoholic Fatty Liver Disease; Particle Size; Sirolimus; TOR Serine-Threonine Kinases; Transcriptional Activation; Up-Regulation; Upstream Stimulatory Factors

Polymyositis (PM) is a chronic disease characterized by muscle pain, weakness, and increase in muscle-related enzymes, accompanied with inflammations in lymphocytes. However, it is not well understood how the molecular alternations in lymphocytes contribute to the development of polymyositis. The mechanistic target of rapamycin (mTOR) signaling is the central regulator of metabolism and inflammation in mammalian cells. Based on previous studies, we proposed that mTOR signaling may control inflammatory reactions

Topics: Biomarkers; Cells, Cultured; Fatty Acids, Monounsaturated; Humans; Leukocytes, Mononuclear; Lipid Metabolism; Molecular Targeted Therapy; Polymyositis; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases