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 hepatocy te growth factor (dHGF) on lipid metabolism in rats. In primary cultured ra t hepatocytes, dHGF accelerated incorporation of [C-14]acetate into cellula r 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 re sults suggest that dHGF stimulates hepatocyte lipogenesis through upregulat ion of the pentose pathway and NADPH formation. Injection of dHGF into norm al rats induced elevation of the serum triglyceride, phospholipid and chole sterol levels dose-dependently and in the same time course as the liver gro wth. dHGF injections stimulated the [C-14]acetate incorporation into the li ver lipids, but not into the adipose tissue nor the small intestine. Serum very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) level s were elevated by dHGF injections. [C-14]Leucine incorporation into VLDL a nd LDL was also increased by dHGF injections. In rats with alcohol-induced fatty livers, dHGF treatment markedly diminished the accumulated liver trig lyceride, while elevating serum lipid concentrations. The present results i ndicate that dHGF stimulates exclusively hepatic lipogenesis and increases serum lipoprotein levels in rats. (C) 2000 Academic Press.