IGFBP2: a possible molecular link between liver, heart, and bloodstream during metabolic dysfunction-associated steatotic liver disease

Introduction and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide, the concomitant presence of fibrosis is considered the most important risk factor of cardiovascular death. IGFBP2 is expressed mainly in the liver and at very low levels in heart. This peptide is associated with metabolic affection including obesity and type 2 diabetes. IGFBP2 role in MASLD is not clear. We aimed to assess the expression of IGFBP2 protein in the liver and associate it with its blood levels and cardiac expression in a rodent model of MASLD. Materials and Patients: Male C57BL/6 mice weighing 23±2g were included and fed a high-fat diet with water added with sugar (HF-SF) or control diet up to 30 weeks. Liver damage was assessed by biopsy. IGFBP2 was assayed by ELISA in serum, liver, and heart. Data is shown as Mean±SD, analyzed by ANOVA, p<0.05. Results: HF-SF mice exhibited increased bodyweight, visceral adiposity, and fasting glycemia compared to controls. HF-SF group developed steatosis with or without fibrosis. Mice showing fibrosis were assessed as F1C, portal fibrosis. IGFBP2 was significantly lower in steatosis regardless of the presence of fibrosis, both in serum and liver. Cardiac expression of IGFBP2 was diminished in steatosis with fibrosis compared with controls. Significant, moderate, positive correlations were observed between serum IGFBP2 and its hepatic expression, as well as IGFBP2 cardiac expression. IGFBP2 in serum negatively correlated with visceral adiposity and bodyweight. Conclusions: IGFBP2 expression in liver and heart depends on the stage of MASLD and is associated with visceral adiposity. IGFBP2 in the bloodstream is produced mainly by the liver, and with lower contribution from heart. Serum IGFBP2 can be considered as a marker of its hepatic and cardiac expressions which are closely related with the stage of MASLD. IGFBP2 might be considered a molecular link between liver and heart during MASLD.