Proteomic analysis to identify differentially expressed proteins between subjects with metabolic healthy obesity and non-alcoholic fatty liver disease

Obese subjects with non-alcoholic fatty liver disease (NAFLD) and considered metabolically healthy have not been well differentiated. In this study, obese subjects were divided into metabolic healthy obesity (MHO) and NAFLD groups. Liver tissues were sampled from these two types of subjects undergoing bariatric surgery, and proteins in the liver tissues that expressed differently between the two groups of subjects were identified by Tandem Mass Tags (TMT) assay. Compared with the MHO group, 132 proteins were found to be upregulated and 84 proteins were found to be downregulated (mainly localized in mitochondria) in NAFLD group. The KEGG pathway analysis showed that significantly upregulated metabolic pathways include PPAR signaling, ECM-receptor interaction and oxidative phosphorylation was significantly downregulated. The GO analysis revealed that upregulated proteins were involved in extracellular structure organization, extracellular matrix organization and downregulated proteins took part in the oxidation–reduction process and so on. FBLN5 and DHRS2 were further validated by Western blot, immunohistochemistry and ELISA. All results demonstrate that FBLN5 expression was significantly upregulated but DHRS2 was significantly downregulated. The variation between MHO and NAFLD was studied by mass spectroscopy to evaluate the mechanism with which MHO subjects resist the harmful effects induced by obesity.