Serum and liver proteome in women with morbid obesity and metabolic dysfunction-associated steatotic liver disease

Abstract Objectives This study aimed to characterize proteome in serum and liver samples from women with morbid obesity (MO) and metabolic dysfunction-associated steatotic liver disease (MASLD) to identify proteins and metabolic pathways. Methods HPLC-MS/MS proteomics was performed on serum and liver samples from 174 women with MO, classified by hepatic histology into three group: normal liver (NL, n=44), simple steatosis (SS, n=66) and metabolic dysfunction-associated steatohepatitis (MASH, n=64). All MASH cases presented mild-moderate hepatic inflammation without fibrosis. Results Serum proteomics identified 257 proteins. In MASLD group, we found most increased levels (log2FC>1.6) of fructose-bisphosphate aldolase, clusterin and collectin-10, and most decreased levels (log2FC < −1.6) of Adiponectin and sex hormone-binding globulin compared with NL group. These proteins were mainly linked to three complement cascade pathways: regulation (33.33 %), initiation (33.33 %) and activation (33.33 %). Liver proteomics identified 2,081 proteins. Comparative liver proteomics between MASLD, SS or MASH groups and NL did not reveal significant differences. However, comparison between MASH and SS identified 72 significantly upregulated and 84 downregulated proteins. Biological processes enrichment analysis of these protein groups revealed that these proteins were mainly involved in these pathways: amino acid metabolism (31.25 %), antimicrobial defense (20 %) and fatty acid metabolism (17.5 %) and others. Conclusions This study identifies serum and liver proteome that could be associated with MASLD and MASH. The study of these proteins and their associated metabolic pathways may be useful for physiopathological research. These findings warrant further validation in independent and diverse cohorts.