Reading the glycome in MASLD: at the crossroads of metabolism and inflammation.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as the hepatic expression of a broader cardiometabolic and inflammatory disorder. In this context, circulating glycoprotein signals may provide information beyond conventional assessment of steatosis and fibrosis risk. García-Mateo et al. evaluated plasma Glyc-A, Glyc-B and Glyc-F using nuclear magnetic resonance in patients with inflammatory bowel disease (IBD), with and without MASLD, and in matched controls. Glycoprotein concentrations showed a progressive increase from controls to IBD and were highest when IBD and MASLD coexisted, while Glyc-B and Glyc-F remained independently associated with MASLD after adjustment for relevant metabolic variables. These findings should not yet be interpreted as establishing new clinical biomarkers. Rather, they raise a more fundamental question: what biological information is captured by circulating glycoprotein signals? Glyc-A, Glyc-B and Glyc-F represent composite spectroscopic signals influenced by acute-phase proteins, systemic inflammation, metabolic dysfunction and, potentially, disease-specific glycan changes. Their interpretation is therefore particularly relevant in IBD, where immune-mediated inflammation may modify the metabolic and hepatic phenotype. Emerging transcriptomic and glycomic data suggest that MASLD arising in different inflammatory contexts may not be biologically identical, despite a similar clinical classification. The current evidence supports the biological plausibility of glycoprotein profiling but not yet its routine clinical use. Future studies should determine the relative contribution of systemic inflammation, adiposity, insulin resistance, dyslipidaemia and liver injury to these signals; establish their relationship with clinically relevant liver phenotypes, particularly fibrosis; and demonstrate incremental value beyond established non-invasive tools. Learning to interpret the glycome may ultimately prove more informative than simply measuring it.