Matched liver-serum multi-omics and genetic risk reveal hepatic compartmentalization of metabolic disease in severe obesity

Hepatic and serum metabolite levels show weak correlation, with liver metabolites more strongly associated with steatosis and inflammation than serum metabolites in severe obesity.

• Why it matters: Understanding the relationship between circulating metabolites and liver pathology is crucial for improving non-invasive diagnosis and understanding metabolic disease mechanisms in obesity.
• What they did: The study profiled hepatic transcriptome, lipidome, and metabolome, along with serum metabolome, in 211 participants, analyzing paired liver and serum samples for metabolite correlations and associations with liver disease features.
• The result: Liver metabolites, especially amino acids, are linked to inflammation independently of serum levels, and circulating metabolites poorly reflect hepatic pathology, emphasizing the need for histological validation over serum measures.