Parasite-induced anorexia: leptin, insulin and corticosterone responses toinfection with the nematode, Nippostrongylus brasiliensis

The nematode parasite, Nippostrongylus brasiliensis, induces a biphasic ano rexia in its rat host. The mechanisms, underlying this anorexia and its pos sible advantages to the host or parasite are unknown. We have investigated the effect of acute (12-24 h) and chronic (2-17 days) infections on plasma concentrations of leptin, insulin and corticosterone, and on hypothalamic e xpression of neuropeptide Y, galanin and corticotrophin-releasing factor ge nes. Plasma leptin was elevated in infected rats relative to uninfected ad libitum-fed controls and pair-fed controls in 12 h infections initiated at dark onset and in infections of 2 days' duration. At other times prior to p arasite expulsion, plasma leptin in infected and pair-fed rats was lower th an that of uninfected ad libitum-fed controls, reflecting the existing stat e of negative energy balance. Elevated plasma leptin concentrations in infe cted rats at day 2 post-infection were accompanied by reduced neuropeptide Y gene expression in the hypothalamic arcuate nucleus compared with both ad libitum control and pair-fed animals, and by lowered corticotrophin-releas ing factor gene expression in the paraventricular nucleus relative to pair- feds. Twelve hour infections were characterized by a substantial increase i n plasma corticosterone that was independent of reduced food intake, and in 12 h infections initiated at dark onset, where plasma leptin was elevated, there was also increased plasma insulin concentration in infected rats. In longer infections, differences between the groups in plasma insulin and co rticosterone concentration were only observed at day 4 post-infection. In s ummary, perturbations to leptin, insulin and corticosterone signals early i n infection map have a causative role and might feed back onto hypothalamic gene expression, whereas subsequent changes in these parameters are more l ikely to be secondary to negative energy balance.