Leptin is an adipokine that plays an important role in the regulation of energy homeostasis. The failure of endogenous and exogenous leptin to mediate its effects (for example, at suppressing appetite and decreasing body weight) has been termed leptin resistance. Hyperleptinemia and leptin resistance can be well demonstrated in animals in which obesity is induced by consumption of a palatable, high-calorie diet (e.g., cafeteria diet-induced obesity). Since leptin receptor signaling is known to be impaired in the hypothalamic arcuate nucleus (ARC) of obese rodents, we investigated the effect of leptin on nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reactivity in the ARC of male Wistar rats with cafeteria diet-induced obesity. Our results have shown that after intraperitoneal administration of leptin, the number of NADPH-d positive neurons in the ARC was significantly lower in obese rats compared with that observed in normal weight rats. Additionally, we have found that leptin-induced NADPH-d staining in ARC neurons and the adjacent ependyma was decreased in obese rats. The results presented here suggest that the ability of leptin to activate nitric oxide synthase in neurons within the ARC as well as tanycytes and ependymal cells of the third ventricle is reduced in rats made obese by a cafeteria diet. We speculate that impairment in leptin-induced NO production presents a potential mechanism, involved in the pathogenesis of obesity and obesity-related disease states.

瘦素是一种脂肪因子，在调节能量稳态中起重要作用。内源性和外源性瘦素无法调节其作用（例如，抑制食欲和减轻体重）被称为瘦素抵抗。高瘦素血症和瘦素抵抗可以在动物中得到很好的证明，其中肥胖是通过食用可口的高热量饮食（例如，食堂饮食诱导的肥胖）引起的。由于已知瘦素受体信号在肥胖啮齿动物的下丘脑弓状核 (ARC) 中受损，我们研究了瘦素对自助餐厅饮食的雄性 Wistar 大鼠 ARC 中烟酰胺腺嘌呤二核苷酸磷酸-心肌黄酶 (NADPH-d) 反应性的影响-诱发肥胖。我们的结果表明，腹腔注射瘦素后，与在正常体重大鼠中观察到的相比，肥胖大鼠 ARC 中 NADPH-d 阳性神经元的数量显着减少。此外，我们发现瘦素诱导的 ARC 神经元和相邻室管膜中的 NADPH-d 染色在肥胖大鼠中减少。这里呈现的结果表明，瘦素激活 ARC 内神经元中的一氧化氮合酶以及第三脑室的长红细胞和室管膜细胞的能力在因食堂饮食而变得肥胖的大鼠中降低。我们推测，瘦素诱导的 NO 产生受损是一种潜在的机制，涉及肥胖和肥胖相关疾病的发病机制。我们发现瘦素诱导的 ARC 神经元和相邻室管膜中的 NADPH-d 染色在肥胖大鼠中减少。这里呈现的结果表明，瘦素激活 ARC 内神经元中的一氧化氮合酶以及第三脑室的长红细胞和室管膜细胞的能力在因食堂饮食而变得肥胖的大鼠中降低。我们推测，瘦素诱导的 NO 产生受损是一种潜在的机制，涉及肥胖和肥胖相关疾病的发病机制。我们发现瘦素诱导的 ARC 神经元和相邻室管膜中的 NADPH-d 染色在肥胖大鼠中减少。这里呈现的结果表明，瘦素激活 ARC 内神经元中的一氧化氮合酶以及第三脑室的长红细胞和室管膜细胞的能力在因食堂饮食而变得肥胖的大鼠中降低。我们推测，瘦素诱导的 NO 产生受损是一种潜在的机制，涉及肥胖和肥胖相关疾病的发病机制。