MECHANISMS OF INCREASED LIPOPROTEIN-LIPASE IN FAT-CELLS OF OBESE ZUCKER RATS

The mechanisms underlying the increased activity of lipoprotein lipase (LPL) in adipocytes of genetically obese Zucker rats was studied. Relative rates of LPL synthesis (percent of total protein synthesis) determined by biosynthetic labeling and specific immunoprecipitation were similar in isolated fat cells from lean and obese rats, in the absence or presence of insulin. Insulin stimulated LPL synthesis as a result of a general increase in protein synthesis, and this effect was more marked in the obese fat cells. Levels of LPL mRNA, as a percent of total RNA, were also similar in fat cells from lean and obese rats. In contrast, when the data are calculated on a per fat cell basis, rates of LPL synthesis per fat cell are ninefold higher in obese compared with lean cells, accounting for the increase in LPL activity per fat cell. Fat cells from lean and obese rats showed similar rates of binding and degradation of purified bovine milk I-125-labeled LPL per unit fat cell surface area. Thus, on a per cell basis, rates of LPL turnover are increased in enlarged Zucker rat adipocytes, but there is no specific abnormality in the cellular regulation of LPL. Increases in LPL activity in obese rat adipocytes are related to an overall hyperresponsiveness to insulin effects on protein synthesis.