Processed silkworm powder (Hongjam) ameliorates metabolic dysfunction-associated steatotic liver disease via GPR35/PKA and SIRT1/AMPK pathways.

INTRODUCTION

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic metabolic disorder linked to obesity, insulin resistance, and type 2 diabetes. This study aimed to investigate the preventive effects of Hongjam, a processed silkworm powder, in a high-fat diet-induced MASLD mouse model and to explore its underlying mechanisms.

METHODS

C57BL/6J mice were fed a high-fat diet with or without Hongjam supplementation. Serum lipid and glucose levels, hepatic lipid accumulation, liver injury markers, and inflammatory responses were evaluated. Mechanistic analyses focused on SIRT1/AMPK signaling, lipogenic and fatty acid oxidation gene expression, STAT3 phosphorylation, cytokine production, and GPR35/PKA-mediated gluconeogenesis. To identify bioactive components, a silk-derived fibroin peptide was synthesized and tested in palmitate-treated HepG2 cells.

RESULTS

Hongjam supplementation improved serum triglyceride, cholesterol, and glucose levels, reduced hepatic lipid accumulation, and lowered liver injury markers. These beneficial effects were associated with activation of the SIRT1/AMPK pathway, suppression of lipogenesis, and enhancement of fatty acid oxidation. Hongjam also attenuated hepatic inflammation by inhibiting STAT3 phosphorylation and reducing pro-inflammatory cytokines, while restoring gluconeogenic capacity through GPR35/PKA signaling. The fibroin peptide suppressed SREBP1 expression, reduced lipid accumulation, and reactivated SIRT1/AMPK and GPR35/PKA/CREB pathways in HepG2 cells.

DISCUSSION: These findings suggest that Hongjam and its fibroin-derived peptide exert protective metabolic effects by modulating lipid metabolism, inflammation, and glucose homeostasis. Together, they highlight the potential of Hongjam as a functional food ingredient for the prevention of MASLD.