Impaired liver regeneration by β-glucosylceramide is associated with decreased fat accumulation.

Objective: To investigate the effect of β-glucosylceramide (GC), a natural glycolipid, on hepatic fat accumulation and regenerative response after partial hepatectomy (PH).

Methods: Male C57Bl/6 mice were assigned to either 70% PH or sham surgery after receiving daily intraperitoneal injection of GC or vehicle for 3 days. Hepatic fat accumulation, cytokines, cell cycle proteins and adipogenic genes expression were assessed at various time points after PH.

Results: The administration of GC delayed hepatic triglyceride accumulation during hepatic regeneration. This observation was closely correlated with alterations in the expression of four major adipogenic genes during the course of liver regeneration, with reduced expression 3 h after PH and increased expression 48 h post-surgery. GC significantly reduced hepatocellular proliferation 48 h after PH. In GC-treated mice, both tumor necrosis factor-α and interleukin-6 levels were lower 3, 48 and 72 h after PH compared with the control group.

Conclusions: Administration of GC delayed hepatic triglyceride accumulation and suppressed early adipogenic gene expression during the hepatic regenerative response. These changes are closely associated with early inhibition of liver regeneration and temporal alteration of cytokine secretion.