LEPTIN REGULATION BY GLUCOSE, CATECHOLAMINES, AND GLUCOCORTICOIDS IN THE TILAPIA AND ITS IMPLICATIONS TO THE VERTEBRATE STRESS RESPONSE

Leptin is a cytokine critical for regulating energy expenditure in vertebrates, yet little is known about how the hormone interacts with the endocrine stress axis, particularly in fishes and other ectotherms. Previous studies in tilapia have shown that leptin A (LepA) is the dominant form of leptin and that its mRNA levels in the liver acutely rise with systemic glucose during seawater challenge, as well as under hypoxic conditions in other fishes. The hormone increases plasma glucose and decreases liver glycogen in vivo in tilapia, suggesting it promotes glycogenolysis. These data suggest that LepA may be involved in the adaptive stress response by mobilizing energy reserves, namely carbohydrates. Currently the regulatory interactions between the classical stress hormones (e.g. cortisol, epinephrine), metabolites (e.g. glucose), and leptin is unclear.

We evaluated the actions of epinephrine, cortisol, and glucose in regulating LepA in the liver, the major site of hormone production in the tilapia (Oreochromis mossambicus). Using hepatocyte incubations and a homologous LepA ELISA, we show that LepA synthesis and secretion declines as ambient glucose levels increase (10-25 mM). These data suggest a negative feedback inhibition whereby leptin stimulates glucose release (glycogenolysis) during the initial stress response and glucose subsequently acts to inhibit leptin synthesis and secretion (Figure 1). Cortisol at physiological concentrations (100 nM) stimulated hepatic lepa mRNA and LepA secretion. Epinephrine, a major adrenergic stress hormone, stimulates LepA secretion in a dose-dependent fashion within 15 minutes, but had little effect on lepa mRNA expression in hepatocytes. The response was accompanied by increases in glucose release likely indicating a classical glycogenolytic effect of the adrenergic hormone. These data suggest hepatic LepA is sensitive to ambient glucose and is stimulated by both catecholamines and glucocorticoids. The results indicate that leptin plays an integral role in the vertebrate stress response to promote energy mobilization in conjunction with the classical stress hormones.