We have established primary cultures of fetal hepatocytes and of precursor adipocytes derived from the genetically obese rat strain. The morphological characteristics and functional capacities of these cells are under study in an effort to identify the locus of action of the fa gene, which is responsible for the development of obesity in the homozygous recessive Zucker rat (fafa). Measurement of lipogenesis by the incorporation of (3H)H20 into total extractable lipid has shown that fetal hepatocytes derived from fatty-fathered litters synthesize less lipid over a 24-hour period than do cells derived from homozygous lean animals. Further studies will establish the hormone responsiveness of fatty vs. lean liver cells. Precursor adipocytes (defined as those cells separated from the the stromal-vascular fraction of adipose tissue that accumulate substantial lipid over 10-12 days in primary culture) derived from lean and obese Zucker rat adipose tissue grow similarly in Dulbecco's modified Eagle's medium supplemented with glucose and insulin. Enzymatic activities and hormonal responsiveness of these cells during the lipid-accumulating phase are being established. Characterization of the metabolic behavior of these cells in culture, particularly their lipogenic-lipolytic activity may aid our understanding of the genetic lesion wich results in obesity in this animal model. Elucidation of the etiology of hyperplastic obesity in the Zucker rat may aid our understanding of the simlar syndrome seen in human obesity of early onset.