At present, LCN2 should be primarily considered a marker of systemic inflammatory burden and disease severity, and its potential as a therapeutic target warrants further investigation in mechanistic and interventional studies
Gaetano Pacinella et al.
The investigators conducted a cross-sectional study involving 40 patients with recently diagnosed MASLD and 40 age- and sex-matched control participants without liver disease. They measured circulating LCN2 levels together with endothelial function using the reactive hyperemia index (RHI), myocardial mechano-energetic efficiency (MMEE), and cognitive performance using the Mini-Mental State Examination (MMSE). Compared with controls, patients with MASLD had significantly higher LCN2 concentrations, poorer endothelial function, lower myocardial mechano-energetic efficiency, and lower MMSE scores. Even after adjustment for age, body mass index, and diabetes, MASLD remained independently associated with elevated LCN2 levels, impaired endothelial function, and reduced cognitive performance.
To better understand these associations, the researchers performed additional analyses to determine whether LCN2 itself independently predicted vascular dysfunction or cognitive impairment. Although LCN2 levels were significantly higher in patients with MASLD, the relationships between LCN2 and vascular or cognitive measures were no longer statistically significant after accounting for major cardiometabolic risk factors. These findings suggest that elevated LCN2 primarily reflects the broader metabolic and inflammatory burden associated with MASLD rather than acting as a direct cause of cardiovascular or neurological dysfunction.
The findings also reinforce the concept that MASLD affects multiple organ systems. In addition to liver disease, patients demonstrated evidence of endothelial dysfunction, subtle cardiac functional impairment, and early cognitive changes. The authors suggest that chronic low-grade inflammation, insulin resistance, adipose tissue dysfunction, and vascular injury likely interact to drive these systemic complications, highlighting the importance of evaluating cardiovascular and neurological health alongside liver disease in patients with MASLD.
