Liver-Pancreas Fat Deposition: Impact on Cardiometabolic Multimorbidity and Cardiac Dysfunction

Area of Science:

• Cardiology
• Hepatology
• Metabolic Diseases

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) and pancreatic steatosis (PS) are linked to cardiometabolic issues.
• The combined impact of MASLD and PS on long-term cardiometabolic multimorbidity (CMM) and cardiac remodelling is not well understood.

Purpose of the Study:

• To investigate the association between PS and MASLD histology severity.
• To evaluate the long-term risk of CMM and cardiac alterations in individuals with single-organ versus dual-organ steatosis (MASLD and PS).
• To explore potential molecular pathways involved in dual-organ steatosis.

Main Methods:

• Cross-sectional analysis of PS and MASLD histology in a biopsy-proven cohort.
• UK Biobank cohort analysis (n=16,408) assessing incident CMM and cardiac magnetic resonance (CMR) findings over a median 5.6-year follow-up.
• Exploratory proteomic profiling to identify molecular pathways.

Main Results:

• PS correlated with more severe MASLD histology, including steatosis, inflammation, and fibrosis.
• Coexisting MASLD and PS additively increased the risk of new-onset CMM (HR=2.013).
• Dual-organ steatosis was linked to increased left ventricular mass and impaired cardiac function, with proteomic analysis revealing upregulated lysosomal and glycosaminoglycan-degrading pathways.

Conclusions:

• Pancreatic steatosis is associated with more severe liver disease histology.
• Concomitant MASLD and PS significantly elevate the risk of cardiometabolic multimorbidity and cardiac remodelling.