Calorie restriction mitigates steatotic liver disease in obese rats after bariatric surgery.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rising alongside the global obesity epidemic. Current therapeutic strategies for MASLD include dietary modification, physical activity, and bariatric surgery. In this study, we established a rat model of morbid obesity plus MASLD to investigate the effects of sleeve gastrectomy (SG) combined with a calorie-restricted diet (CRD) on metabolic and hepatic outcomes. Obesity and hepatic steatosis were induced in male Wistar rats and subsequently SG was performed. Postoperatively, the rats received either a high-fat diet (HFD) or CRD for 18 weeks. Blood and liver tissue samples were analyzed using lipidomics, histopathology, and protein expression profiling to assess metabolic, inflammatory, and fibrotic changes. The HFD led to weight gain, dyslipidemia, hepatic lipid accumulation, and upregulation of fibrosis-related proteins, including transforming growth factor-β1, collagen I, and α-smooth muscle actin. Although SG partially improved some metabolic parameters in the HFD group, it failed to reverse hepatic steatosis and fibrosis sustainably. CRD significantly reduced serum triglyceride and cholesterol concentrations as well as hepatic lipid content and fibrosis-related protein expression. CRD intake exerted the protective effects against hepatic steatosis and fibrosis, emerging as an effective adjunct to bariatric surgery for managing obesity-related MASLD. Lipidomic analysis revealed significantly altered plasma and hepatic concentrations of diacylglycerol 38:2, indicating its potential as an early lipid-based biomarker of MASLD-related metabolic dysregulation. Our results revealed that SG, combined with an 18-week CRD intake, effectively prevented MASLD progression by reducing hepatic lipid accumulation, inflammatory cytokine expression, and activation of fibrosis-related proteins.