Abstract: | BACKGROUND: Thyroid-stimulating hormone (TSH) plays an important role in the regulation of lipid metabolism. However, little is known about the role that exosomes play in the process of TSH-induced lipotoxicity in non-alcoholic fatty liver disease (NAFLD). As a preliminary step, the present study set out to investigate alterations in protein expression in exosomes derived from TSH-stimulated HepG2 cells. METHODS: HepG2 cells were treated with TSH, exosomes were collected, and proteins were identified by mass spectrometry (MS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were performed to analyze the identified proteins. RESULTS: TSH treatment significantly increased exosomal production and changed the exosomal proteomic profile in HepG2 cells. Among the 1728 proteins, 140 identified proteins were upregulated and seven proteins were downregulated. GO analysis and KEGG analysis revealed that these proteins were involved in multiple processes including metabolism, apoptosis, and inflammation. CONCLUSION: Our preliminary study demonstrated that exosomes derived from TSH-stimulated hepatocytes were increased and showed a specific altered spectrum of proteins, many of which were involved in metabolism, signal transduction, apoptosis, and inflammation. This study offers new insights into the pathogenesis of TSH-induced lipotoxicity in NAFLD. |