HORMONAL-REGULATION OF HORMONE-SENSITIVE LIPASE ACTIVITY AND MESSENGER-RNA LEVELS IN ISOLATED RAT ADIPOCYTES

Hormone-sensitive lipase (HSL) mediates the lipolysis of triacylglycer ol from mammalian adipocytes, resulting in the release of non-esterifi ed fatty acids and glycerol. Although numerous studies have examined t he hormonal regulation of HSL, the measurement of HSL mRNA levels in r esponse to hormonal regulators has not been studied. This study was de signed to determine the effects of epinephrine, growth hormone, glucag on, and dexamethasone on HSL expression by measuring HSL mRNA levels a nd glycerol release in primary cultures of rat adipocytes. Exposure of adipocytes to epinephrine at 10(-7) M and 10(-5) M for 4 h resulted i n an increase in medium glycerol (209 +/- 46%, and 284 +/- 58% of cont rol, P < 0.001, respectively). However, no change in HSL mRNA levels o ccurred due to the epinephrine treatment. Similarly, the peptides gluc agon (10(-7) M and 10(-5) M for 4 h) and growth hormone (100 ng/ml for 24 h) resulted in increased medium glycerol and had no effect on HSL mRNA levels in adipocytes. Dexamethasone was added to adipocyte cultur es for 4 and 24 h, and resulted in a dose-dependent increase of medium glycerol (102 +/- 8%, 138 +/- 8% (P < 0.001), and 168 +/- 24% (P < 0. 001) for 10(-8) M, 10(-7) M, and 10(-6) M, respectively). In contrast to the other hormones, however, dexamethasone yielded increases in HSL mRNA levels of 368 +/- 87% and 452 +/- 29% of control at 10(-7) M and 10(-6) M, respectively. Thus, epinephrine, glucagon, and growth hormo ne increased the activity of HSL when added to primary cultures of adi pocytes through post-transcriptional mechanisms, and not through a cha nge in HSL mRNA level. Dexamethasone, however, increased HSL mRNA leve ls by approximately 4-fold, and this study represents the first demons tration of HSL mRNA regulation in adipose tissue.