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

Hormone-sensitive lipase (HSL) mediates the lipolysis of triacylglycerol from mammalian adipocytes, resulting in the release of non-esterified fatty acids and glycerol. Although numerous studies have examined the hormonal regulation of HSL, the measurement of HSL mRNA levels in response to hormonal regulators has not been studied. This study was designed to determine the effects of epinephrine, growth hormone, glucagon, and dexamethasone on HSL expression by measuring HSL mRNA levels and 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 in an increase in medium glycerol (209 +/- 46%, and 284 +/- 58% of control, P < 0.001, respectively). However, no change in HSL mRNA levels occurred due to the epinephrine treatment. Similarly, the peptides glucagon (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 cultures 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 hormone increased the activity of HSL when added to primary cultures of adipocytes through post-transcriptional mechanisms, and not through a change in HSL mRNA level. Dexamethasone, however, increased HSL mRNA levels by approximately 4-fold, and this study represents the first demonstration of HSL mRNA regulation in adipose tissue.