data availability .xlsx

Leptin is an adipokine, involved in the regulation of energy balance and immune function. Peripheral administration of leptin has been demonstrated to elicit a prostaglandin E2-dependent fever in rats. Previous studies have reported that nitric oxide, produced by neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS), and hydrogen sulfide, produced by cystathionine γ-lyase (CSE), play an important role for the induction of fever to lipopolysaccharide. To investigate the role of nNOS, iNOS and CSE in the effect of leptin on body temperature (Tb), we used the selective nNOS inhibitor 7-nitroindazole (7-NI), the selective iNOS inhibitor aminoguanidine (AG) and the CSE inhibitor dl-propargylglycine (PAG). The results of the first series of experiments demonstrated that intraperitoneal (i.p.) administration of leptin (0.5 mg/kg) induced a significant increase in Tb, whereas i.p. administration of AG (50 mg/kg), 7-NI (10 mg/kg) or PAG (50 mg/kg) did not induce any changes in Tb of rats. In the second series of experiments, we found that i.p. administration of AG, 7-NI or PAG 10 min before leptin abolished the increase in Tb, elicited by leptin. These results suggest the involvement of iNOS, nNOS and CSE in leptin-induced febrile response. In this study, we also investigated the interaction between leptin and each of the inhibitors through an examination of their effect on food consumption and body weight gain following their coadministration. We showed that leptin, AG, 7-NI and PAG, administered alone, suppressed food intake and body weight gain in rats at 24 h after the injection. Coadministration of leptin with AG, 7-NI or PAG did not produce any additive or synergistic effects on food intake and body weight.