Evidence for a sustained genetic effect on fat storage capacity in cultured adipose cells from Zucker rats.

Using mature adipocytes and preadipocytes from genetically obese Zucker rats, we investigated the cells' ability to maintain abnormal fat storage capacity when withdrawn from their in vivo environment. Long-term adipocyte cultures from obese rats displayed an increase in both glucose consumption (GC) and enzyme activities, including fatty acid synthase (4-fold), glycerol-3-phosphate dehydrogenase (4.5-fold), lipoprotein lipase (LPL; 6-fold), and malic enzyme (2.5-fold). Fully differentiated obese predipocytes exhibited a twofold increase in these enzyme activities, together with higher glucose metabolism. In obese cells, LPL mRNA was increased in both adipocytes (6-fold) and differentiated preadipocytes (2-fold). Insulin mediated an increase in GC and lipogenic enzymes in both adipocytes and preadipocytes regardless of the genotype; this effect was more marked in obese cells. Examining cultured adipocytes from rats fed a high-fat diet, we showed that the nutritional effect upon GC and lipogenic enzymes was abolished after culture. These results demonstrated that fatty mutation may be intrinsically expressed in prolonged cultured mature adipocytes and in newly differentiated adipocytes.