The effect of high-fat diet on the sphingolipid pathway of signal transduction in regenerating rat liver.

Liver regeneration after partial hepatectomy (PH) is achieved by intense cells proliferation. Sphingosine-1-phosphate stimulates proliferation but ceramide and sphingosine induce apoptosis. The aim of the study was to investigate the influence of high-fat diet (HFD) on the sphingolipid metabolism during the first 24h of liver regeneration in rats. Rats were fed HFD or standard diet for 7 days prior to the PH. The content of sphingolipids and the activity of sphingomyelinases (n and aSMase), ceramidases (n and aCDase) and sphingosine kinase (SPHK) were measured. It has been found that HFD increased the activity of aSMase and nCDase at 4th hour after PH. The content of ceramide and sphingosine decreased in HFD group at each time point. This was accompanied by elevated content of sphingosine-1-phosphate and sphinganine-1-phosphate. Decrease in SPHK activity in cytosol after partial hepatectomy was inversely correlated (r=-0.7538) with increase in S1P, which suggest translocation of SPHK to plasma membrane. Shingosine-1-phosphate to ceramide ratio was higher in rats fed HFD. It is concluded that HFD stimulates the pro-mitotic action of the sphingolipid signaling in regenerating rat liver.