Skeletal muscle as a source of IGFBP-2 in a murine model of metabolic dysfunction associated with steatotic liver disease.

Introduction and Objectives

Insulin-like Growth Factor Binding Protein (IGFBP)-2 is lower in serum during obesity and metabolic dysfunction. We have previously shown that the decrease in serum IGFBP-2 follows a diminished expression in liver and heart, both associated with the progression of steatotic liver disease. We aimed to identify, in a murine model, the synthesis of IGFBP-2 in extrahepatic tissues involved in metabolic dysfunction: skeletal muscle and adipose tissue.

Materials and Patients

Samples of hamstring muscle, and epididymal adipose tissue were obtained from male C57BL/6 mice, fed a high-fat diet supplemented with sucrose and fructose (42g/L) in the beverage during 6 months. All procedures were approved by the Institutional Committee of Care and Use of Laboratory Animals at the School of Medicine, UNAM (FM/DI/005/2022). Four groups were included: Control; Metabolic dysfunction (MD), exhibiting increased bodyweight and adiposity; MD with steatosis (MD+SS); and MD+SS with fibrosis (MD+SS+F). Total protein was isolated in a protease inhibitor cocktail. Protein integrity was assessed by SDS-PAGE. IGFBP-2 was assayed by ELISA. Data was shown as Mean±SD, analyzed by one-way ANOVA; Student´s t test was applied to compare 2 groups. P<0.05 was considered significant.

Results

IGFBP-2 expression was 6-fold increased in control skeletal muscle compared to control adipose tissue. In epididymal adipose tissue, IGFBP-2 expression significantly decreased in MD+SS+F compared to Controls, and MD. In contrast, the hamstring showed increased IGFBP-2 expression in mice showing metabolic dysfunction associated with steatotic liver disease: MD+SS and MD+SS+F. The percentage of adiposity significantly increased in MD subjects whereas no changes were observed regarding muscle mass, suggesting hypertrophy might be key.

Conclusions

Our results show that metabolic dysfunction (MD) associated with MASLD have a role in inhibiting IGFBP-2 expression in adipose tissue. In contrast, skeletal muscle increases its synthesis. These results suggest a role for skeletal muscle in the reversion of MASLD through IGFBP-2 expression. More studies are needed to identify the roles of skeletal muscle and its hypertrophic state in MASLD.

Ethical statement: All procedures were approved by the institutional Committee for the Care and Use of Laboratory Animals (CICUAL) from the Medicine School, UNAM (FM/DI/005/2022).

Declaration of interests: None.

Funding: This study was supported by the Research Direction from General Hospital of Mexico (DI/12/UME/4/20).