Hypoxemia-induced leptin secretion: a mechanism for the control of food intake in diseased fish

Abstract

Leptin is a potent anorexigen, but little is known about the physiological conditions under which this cytokine regulates food intake in fish. In this study, we characterized the relationships between food intake, O2-carrying capacity, liver leptin-A1 (lep-a1) gene expression, and plasma leptin-A1 in rainbow trout infected with a pathogenic hemoflagellate,Cryptobia salmositica. Aslepgene expression is hypoxia-sensitive andCryptobia-infected fish are anemic, we hypothesized thatCryptobia-induced anorexia is mediated by leptin. A 14-week time course experiment revealed thatCryptobia-infected fish experience a transient 75% reduction in food intake, a sharp initial drop in hematocrit and hemoglobin levels followed by a partial recovery, a transient 17-fold increase inlep-a1gene expression, and a sustained increase in plasma leptin-A1 levels. In the hypothalamus, peak anorexia was associated with decreases in mRNA levels of neuropeptide Y (npy) and cocaine- and amphetamine-regulated transcript (cart), and increases in agouti-related protein (agrp) and pro-opiomelanocortin A2 (pomc). In contrast, in non-infected fish pair-fed to infected animals,lep-a1gene expression and plasma levels did not differ from those of non-infected satiated fish. Pair-fed fish were also characterized by increases in hypothalamicnpyandagrp, no changes inpomc-a2, and a reduction incartmRNA expression. Finally, peak infection was characterized by a significant positive correlation between O2-carrying capacity and food intake. These findings show that hypoxemia, and not feed restriction, stimulates leptin-A1 secretion inCryptobia-infected rainbow trout and suggest that leptin contributes to anorexia by inhibiting hypothalamicnpyand stimulatingpomc-a2.