Epinephrine and glucose regulation of leptin synthesis and secretion in a teleost fish, the tilapia (Oreochromis mossambicus).

Acute stress is regulated through the sympathetic adrenergic axis where catecholamines mobilize energy stores including carbohydrates as a principal element of the endocrine stress response. Leptin is a cytokine critical for regulating energy expenditure in vertebrates and is stimulated by various stressors in fish such as fasting, hyperosmotic challenge, and hypoxia. However, little is known about the regulatory interactions between leptin and the endocrine stress axis in fishes and other ectothermic vertebrates. We evaluated the actions of epinephrine and glucose in regulating leptin A (LepA) in vivo and in vitro in tilapia. Using hepatocyte incubations and a homologous LepA ELISA, we show that LepA synthesis and secretion decline as ambient glucose levels increase (10-25 mM). By contrast, bolus glucose administration in tilapia increases lepa mRNA levels 14-fold at 6 h, suggesting systemic factors regulated by glucose may counteract the direct inhibitory effects of glucose on hepatic lepa mRNA observed in vitro. Epinephrine stimulated glucose and LepA secretion from hepatocytes in a dose-dependent fashion within 15 min but had little effect on lepa mRNA levels. An in vivo injection of epinephrine into tilapia stimulated a rapid rise in blood glucose which was followed by a 4-fold increase in hepatic lepa mRNA levels at 2.5 and 6 h. Plasma LepA was also elevated by 6 h relative to controls. Recombinant tilapia LepA administration in vivo did not have any significant effect on plasma epinephrine levels. The results of this study demonstrate LepA is negatively regulated by rises in extracellular glucose at the level of the hepatocyte but stimulated by hyperglycemia in vivo. Further, epinephrine increases LepA. This, along with previous work demonstrating a hyperglycemic and glycogenolytic effect of LepA in tilapia, suggests that epinephrine may stimulate leptin secretion to augment and fine tune glucose mobilization and homeostasis as part of the integrated, adaptive stress response.