Leptin is a pleiotropic hormone known to influence numerous physiological processes including appetite, energy expenditure, and reproduction in vertebrates. In mammals, leptin is produced by adipose tissue works primarily as an adipostat. It circulates in proportion to fat deposition and inhibits appetite while stimulating lipolysis and fatty acid oxidation to prevent excessive lipid accumulation. Its function on energy homeostasis in fish remains poorly understood despite leptin’s well-conserved anorexigenic actions. Here we discuss the putative function of leptin on metabolism and its implications in the stress response in teleosts fishes through studies in the euryhaline tilapia, Oreochromis mossambicus. The liver is typically the predominate site of production in fishes and data suggests that leptin may act to regulate carbohydrate catabolism in these and other ectothermic vertebrates. Our work in the tilapia shows that recombinant tilapia leptin A (rtLepA), the predominant paralog in fishes, and its mRNA levels in the liver acutely rise with systemic glucose during seawater challenge and increase with fasting as well as under hypoxic conditions. The hormone increases plasma glucose and decreases liver glycogen in vivo in tilapia, suggesting it promotes glycogenolysis. Results suggest that LepA may be involved in the adaptive stress response by mobilizing energy reserves, namely carbohydrates.
Both insulin and the classical stress hormones, epinephrine and cortisol, play roles in regulating glucose availability and interact with leptin in tilapia to maintain glucose homeostasis under normal anabolic states as well as during stress-associated catabolic states. LepA synthesis and secretion from hepatocytes declines as ambient glucose levels increase, suggesting a negative feedback inhibition whereby leptin stimulates glucose release (glycogenolysis) during the initial stress response and glucose subsequently acts to directly inhibit in vitro leptin synthesis and secretion. Cortisol stimulated hepatic LepA secretion and suppressed lepa mRNA in vitro, while epinephrine, a major adrenergic stress hormone, stimulates LepA secretion. 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.
Additional studies utilizing the tilapia pituitary transcriptome identified numerous metabolic pathways regulated by leptin. Orthogonal testing showed the hormone induces glycolysis by increasing the activity of key glycolytic enzymes and their transcript levels. Liver lepa abundance increases with hypoxia in the tilapia and leptin affected hypoxic responsive pathways within the transcriptome likely associated with enhanced anaerobic glycolysis. Collectively, research suggests leptin plays an integral role in conjunction with the classical stress hormones to promote carbohydrate catabolic processes critical to the adaptive stress response in fishes.