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.

瘦素（Leptin）是一种脂肪因子（adipokine），参与机体能量平衡与免疫功能的调控。已有研究证实，外周给予瘦素可诱导大鼠产生依赖于前列腺素E2（prostaglandin E2）的发热反应。既往研究表明，由神经元型一氧化氮合酶（neuronal nitric oxide synthase, nNOS）和诱导型一氧化氮合酶（inducible nitric oxide synthase, iNOS）生成的一氧化氮，以及由胱硫醚γ裂解酶（cystathionine γ-lyase, CSE）生成的硫化氢，在脂多糖（lipopolysaccharide）诱导的发热过程中发挥重要作用。为探究nNOS、iNOS及CSE在瘦素调节大鼠体温（body temperature, Tb）过程中的作用，本研究选用选择性nNOS抑制剂7-硝基吲唑（7-nitroindazole, 7-NI）、选择性iNOS抑制剂氨基胍（aminoguanidine, AG）以及CSE抑制剂dl-炔丙基甘氨酸（dl-propargylglycine, PAG）开展实验。第一组实验结果显示，腹腔内（intraperitoneal, i.p.）给予瘦素（0.5 mg/kg）可显著升高大鼠体温，而单独腹腔给予AG（50 mg/kg）、7-NI（10 mg/kg）或PAG（50 mg/kg）均未对大鼠体温产生明显影响。第二组实验中，我们发现于瘦素给药前10分钟腹腔给予AG、7-NI或PAG，可完全阻断瘦素诱导的体温升高现象。上述结果提示，iNOS、nNOS及CSE均参与了瘦素介导的发热反应。本研究同时通过联合给药实验，探究了瘦素与上述抑制剂之间的相互作用对大鼠摄食量与体增重的影响。结果显示，单独给予瘦素、AG、7-NI或PAG，均可在给药后24小时抑制大鼠的摄食量与体增重；而瘦素与AG、7-NI或PAG联合给药时，未对摄食量与体增重产生任何相加或协同效应。