Dexamethasone stimulates leptin release from human adipocytes: Unexpected inhibition by insulin

Abstract

In the present study we have examined the effect of dexamethasone on ob gene mRNA expression and leptin release from isolated human subcutaneous adipocytes. Dexamethasone stimulated leptin release from cultured adipocytes in a time- and dose-dependent manner. A two-fold increase in leptin release was detectable by 36 h of treatment with 10(-7) M dexamethasone. Leptin release was preceded by a significant 83 +/- 30% increase in ob mRNA after 24 h exposure to the compound. Co-incubation of cells with dexamethasone (10(-7) M) and insulin (10(-7) or 10(-9) M) completely blocked the dexamethasone-stimulated increase in ob mRNA and leptin release. These data demonstrate that insulin and glucocorticoids regulate leptin synthesis and release from human adipocytes in vitro.

TSH stimulates leptin secretion by a direct effect on adipocytes

“…However, there is no support either in experimental animals (Gualillo et al 1999) or in the present work, for a direct PRL action on the adipocyte production of leptin. Similarly, hypercorticoid states are associated with enhanced leptin levels (Leal-Cerro et al 1996, Masuzaki et al 1997 and glucocorticoids are potent inducers of leptin synthesis and secretion at the adipose tissue level (Considine et al 1997, Casabiell et al 1998, but no data link ACTH with a direct action on the adipocyte and the present results also discard that mechanism. Finally, while the action of leptin over gonadotrophin-releasing hormone secretion by the hypothalamus is well supported (Yu et al 1997, Carro et al 1999, Magni et al 1999, no direct interaction between LH or FSH and leptin has been reported previously or observed in this work.…”

“…On theoretical grounds at least, such a control is feasible, as we are now well aware that plasma leptin levels do not just have a stoichiometric relationship with fat mass. On the contrary, leptin levels reflect fat mass plus the action of several circulating hormones and factors, which directly operate on the adipocytes releasing leptin (Considine et al 1997, Casabiell et al 1998.…”

Insulin and (or) dexamethasone effectson leptin production and metabolic activitiesof ovine adipose tissue explants

“…Briefly, tissue LPL activity was measured using an artificial emulsion containing 3 H-triolein after a detergent (DeoxycholateNonidet P40, Sigma Chemical, SaintQuentin-Fallavier, France) extraction procedure. Enzyme activity was expressed in nmoles of released fatty acid·min -1 per gram of tissue.…”

“…III). Indeed, insulin increased [6,7,22] or did not change [3,7,23] leptin production according to the experimental conditions (tissue vs. adipocytes, incubation duration, hormonal concentrations used) but also to adipose depot site and gender.…”

“…In rat or human AT, reports conflict on the respective effects of insulin and dexamethasone (DEX, a synthetic glucocorticoid) on leptin expression, and their interaction. Indeed, there are reports of either an inhibitory [3,4] or a stimulatory [5,6] effect of insulin on glucocorticoid-stimulated leptin mRNA and leptin production by rat or human AT. Furthermore, it was shown that insulin and glucocorticoid have depot-specific effects on leptin expression in human AT [7].…”