Primary cultures of fetal hepatocytes from the genetically obese Zucker rat: Protein synthesis

Summary Primary fetal hepatocytes derived from Zucker rats with expectedfa gene frequencies of 0.0 and 0.75 have been established and can be used to detect early effects of thefa gene on hepatocellular metabolism. Paired incubation experiments demonstrate that protein synthesis in 0.75fa gene cultures is significantly less than in 0.0fa gene cultures under basal conditions. Insulin stimulates protein synthesis in 0.0fa gene cultures but has no effect on 0.75fa gene cultures. Cycloheximide inhibits protein synthesis in both types of culture. NH₄Cl inhibits protein synthesis in 0.0 but not in 0.75fa gene cultures. These data suggest that fetal hepatocytes bearing thefa gene have in vitro a generally sluggish anabolic capacity and a blunted capacity to respond to insulin compared to fetal hepatocytes without thefa gene. These diminished capacities may be expressions of a genetic error in lysosomal function. A portion of this work was presented in preliminary form at the 1980 meeting of the Tissue Culture Association. This work was supported in part by National Institutes of Health Grants AM19382 and AM06197.