THE REGULATION OF LIPOPROTEIN-LIPASE GENE-EXPRESSION BY DEXAMETHASONEIN ISOLATED RAT ADIPOCYTES

Lipoprotein lipase (LPL) is an enzyme found in adipose tissue that is important in the hydrolysis of triglyceride-rich lipoproteins, and in the uptake of FFA lipid into the adipocyte. To examine the effects of glucocorticoids on adipose tissue LPL, male Sprague-Dawley rats were i njected with dexamethasone (1 mg/kg) every other day for 10 days, foll owed by measurement of LPL in epididymal adipose tissue. Compared to s ham-injected controls, heparin-releasable LPL activity and LPL mass in the dexamethasone-treated rats were 44% and 62% of those in control r ats, respectively. Adipocytes were prepared from the fat pads and puls e labeled with [S-35]methionine, demonstrating a decrease in the LPL s ynthetic rate in the treated rats to 57% of the rate in control rats. In addition, LPL mRNA was quantitated by Northern blotting, demonstrat ing a decrease in LPL mRNA in the dexamethasone-treated rats. A simult aneous decrease in the message for gamma-actin was also noted. To exam ine the effects of dexamethasone on LPL in vitro, adipocytes were prep ared from normal rats and treated with dexamethasone for 24 h in vitro . Dexamethasone decreased heparin-releasable LPL activity in cultured adipocytes to 40 +/- 6% of the control value (P < 0.01). This decrease in LPL activity was accompanied by a decrease in the LPL synthetic ra te using [S-35]methionine labeling, to 33% of the control value, and n o specific change in LPL turnover or secretion. In addition, dexametha sone added to adipocytes decreased LPL mRNA levels. Because the combin ation of insulin plus dexamethasone has been shown to yield synergisti c increases in LPL in adipose tissue pieces, insulin was added to isol ated adipocytes in combination with dexamethasone. Whereas insulin and dexamethasone individually had opposite effects on LPL, the combinati on of insulin plus dexamethasone resulted in no change in any aspect o f LPL gene expression. Thus, dexamethasone resulted in a decrease in a dipocyte LPL mRNA levels both when added to cultured adipocytes in vit ro as well as when injected into rats. This decreased LPL mRNA level y ielded corresponding changes in the LPL synthetic rate and LPL activit y.