A deleted form of human hepatocyte growth factor stimulates hepatic lipogenesis and lipoprotein synthesis in rats

Here we report the effect of the recombinant human deleted form of hepatocyte growth factor (dHGF) on lipid metabolism in rats. In primary cultured rat hepatocytes, dHGF accelerated incorporation of [(14)C]acetate into cellular lipids in a concentration-dependent manner. dHGF also increased the gene expression and enzyme activity of glucose-6-phosphate dehydrogenase, a rate-limiting enzyme of the pentose phosphate pathway, in hepatocytes. These results suggest that dHGF stimulates hepatocyte lipogenesis through upregulation of the pentose pathway and NADPH formation. Injection of dHGF into normal rats induced elevation of the serum triglyceride, phospholipid and cholesterol levels dose-dependently and in the same time course as the liver growth. dHGF injections stimulated the [(14)C]acetate incorporation into the liver lipids, but not into the adipose tissue nor the small intestine. Serum very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels were elevated by dHGF injections. [(14)C]Leucine incorporation into VLDL and LDL was also increased by dHGF injections. In rats with alcohol-induced fatty livers, dHGF treatment markedly diminished the accumulated liver triglyceride, while elevating serum lipid concentrations. The present results indicate that dHGF stimulates exclusively hepatic lipogenesis and increases serum lipoprotein levels in rats.