Adipo-neuroinflammation, cognitive impairment and surrogate markers of cardiovascular risk in patients with Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognised as a systemic condition associated with cardiometabolic and neurovascular alterations. Lipocalin-2 (LCN2), a marker of adipo-neuroinflammation, may represent a link between metabolic dysfunction, vascular impairment, and cognitive decline.

Materials and methods: In this cross-sectional study, we enrolled a group of 40 patients with a recent diagnosis of MASLD and a control group of 40 patients with no history of anamnestic or active liver disease. We evaluated serum LCN2 levels, endothelial function assessed by reactive hyperemia index (RHI), myocardial mechano-energetic efficiency (MMEE), and cognitive performance using the Mini-Mental State Examination (MMSE). Multivariable analyses were adjusted for age, BMI, and diabetes mellitus.

Results: Compared with controls, patients with MASLD showed higher LCN2 levels, lower RHI and MMEE values, and lower MMSE scores. MASLD was independently associated with lower RHI, lower MMSE, and higher LCN2 levels in multivariable models. However, additional partial correlation analyses adjusting for major cardiometabolic confounders did not confirm independent associations between LCN2 and vascular or cognitive parameters.

Conclusions: MASLD is associated with endothelial dysfunction, early cognitive changes, and increased LCN2 levels. However, these relationships appear to be largely influenced by the underlying cardiometabolic profile. LCN2 should be interpreted primarily as a marker of systemic metabolic and inflammatory burden rather than as a causal mediator.