Primary cultures of fetal hepatocytes from the genetically obese Zucker rat: characterization and total lipogenesis.

Primary fetal hepatocyte cultures derived from Zucker rats and with expected fa-gene frequencies of 0.0 and 0.75 have been established and can be used to detect early effects of the fa gene on hepatocellular metabolism. Proliferative capacity is similar in both types of culture. Changes of the growth media significantly decrease total lipogenesis in both 0.0 and 0.75 fa-gene culture grown in arginine-free DME medium. Paired incubation experiments demonstrate that total lipogenesis in 0.75 fa gene cultures is significantly less than in 0.0 fa-gene cultures under basal conditions. Stimulation of total lipogenesis by pharmacological doses of insulin and excess substrate (glucose) is significantly less in the 0.75 fa gene than in the 0.0 fa-gene cultures. These data suggest that the development of obesity in the Zucker rat cannot be attributed to elevated hepatic lipogenesis in the fetus.