Comparative Analysis of the Human Proteome Profile in visceral Adipose Tissue and Liver Tissue in Individuals with Obesity With and Without MASLD and MASH

Abstract: Background/Objectives: Visceral adipose tissue (VAT) could be directly involved in the develop- ment of metabolic-associated steatotic liver disease (MASLD) and progression to metabol-ic-associated steatohepatitis (MASH). We employed untargeted proteomics analyses of paired VAT and liver biopsies to explore protein expression patterns in patients with obesity, MASLD and MASH in search of the potential presence of a MASH associated proteome in VAT and liver. Methods: VAT and liver tissue were collected from 70 subjects with severe obesity (SWO) and nine control study subjects without obesity (CON). SWO were stratified on the basis of liver his-tology into LS- (no liver steatosis), LS+ (liver steatosis) and MASH. Peptides were extracted from frozen tissue and were analyzed by liquid chromatography coupled to tandem mass spectrome-try (LC-MS/MS). Raw files were analyzed with Spectronaut, proteins were searched against the human FASTA Uniprot database and the significantly expressed proteins in the two tissues were analyzed. P-values were false discovery rate (FDR) corrected. Results: 59 VAT and 42 liver proteins were significantly differentially expressed between the four groups; LS-, LS+ and MASH and CON. The majority were upregulated, and many were related to lipid metabolism. In VAT only one protein, SQOR, was significantly downregulated in the MASH group only. In liver tissue from patients with MASH six proteins were significantly altered compared with the three other groups. Correlation analyses between the top 10 positive VAT and liver proteins were dominated by inflammatory and detoxification proteins. Conclusions: Presence of MASH is not reflected in the VAT proteome and both the VAT, and the liver proteome are generally affected more by the presence of obesity than by MASLD severity. Several immunomodulating proteins correlated significantly between VAT and liver tissue and could reflect common pathophysiological characteristics. .