Growth hormone alters lipolysis and hormone-sensitive lipase activity in 3T3-F442A adipocytes

While growth hormone (GH) has long been known as a lipolytic hormone, it has been difficult to study the cellular mechanisms for this effect. Since cultured 3T3-F442A adipocytes have recently proven to be useful to study chronic effects of GH on adipocyte metabolism, we examined the effects of GH on lipolysis. In these cells, GH alone produced a dose-dependent increase in the release of glycerol after 24 to 48 hours. The maximum increase occurred with 10 ng/mL human GH. The effect of GH was similar in the presence and absence of dexamethasone. Under each condition, the stimulation of glycerol release was accompanied by a GH-induced increase in the activity of hormone-sensitive lipase (HSL), a key lipolytic enzyme. The increase in HSL required 24 hours with GH and lasted at least 48 hours. The increase in HSL activity by epinephrine, like glycerol release, was potentiated by GH. Although GH potently simulates the activity of the lipogenic enzyme glycerol phosphate dehydrogenase (GPD) in differentiating 3T3-F442A preadipocytes, GH had a negligible effect on GPD activity in the differentiated adipocytes with chronic or short-term incubation. However, in contrast to the chronic effect of GH, short-term (30-minute) incubation with GH inhibited epinephrine-stimulated glycerol release, a characteristic transient antilipolytic effect of GH. These studies indicate that chronic GH treatment is lipolytic in cultured 3T3-F442A adipocytes, and document that lipolytic responses to GH involve an increase in the activity of HSL.