Gautron L, Mingam R, Moranis A, Combe C, Layé S
Laboratoire des Régulations Neuroendocriniennes, EA 2972, Université Bordeaux I, 33400 Talence, France.
Neuroscience. 2005;134(3):933-46. doi: 10.1016/j.neuroscience.2005.03.063.
Fasting attenuates disease-associated anorexia, but the mechanisms underlying this effect are not well understood. In the present study, we investigated the extent to which a 48 h fast alters hypothalamic neuronal activity in response to the anorectic effects of lipopolysaccharide in rats. Male rats were fed ad libitum or fasted, and were injected with i.p. saline or lipopolysaccharide (250 microg/kg). Immunohistochemistry for Fos protein was used to visualize neuronal activity in response to lipopolysaccharide within selected hypothalamic feeding regulatory nuclei. Additionally, food intake, body weight, plasma interleukin-1 and leptin levels, and the expression of mRNA for appetite-related neuropeptides (neuropeptide Y, proopiomelanocortin and cocaine-amphetamine-regulated transcript) were measured in a time-related manner. Our data show that the pattern of lipopolysaccharide-induced Fos expression was similar in most hypothalamic nuclei whatever the feeding status. However, we observed that fasting significantly reduced lipopolysaccharide-induced Fos expression in the paraventricular nucleus, in association with an attenuated lipopolysaccharide-induced anorexia and body weight loss. Moreover, lipopolysaccharide reduced fasting-induced Fos expression in the perifornical area of the lateral hypothalamus. Lipopolysaccharide-induced circulating levels of interleukin-1 were similar across feeding status. Finally, fasting, but not lipopolysaccharide, affected circulating level of leptin and appetite-related neuropeptides expression in the arcuate nucleus. Together, our data show that fasting modulates lipopolysaccharide-induced anorexia and body weight loss in association with neural changes in specific hypothalamic nuclei.
禁食可减轻疾病相关的厌食症，但这种作用的潜在机制尚不清楚。在本研究中，我们调查了48小时禁食在多大程度上改变大鼠下丘脑神经元活动，以应对脂多糖引起的厌食作用。雄性大鼠自由进食或禁食，并腹腔注射生理盐水或脂多糖（250微克/千克）。采用Fos蛋白免疫组织化学法观察选定的下丘脑进食调节核内对脂多糖产生反应的神经元活动。此外，还以时间相关的方式测量了食物摄入量、体重、血浆白细胞介素-1和瘦素水平，以及食欲相关神经肽（神经肽Y、阿黑皮素原和可卡因-安非他明调节转录物）的mRNA表达。我们的数据表明，无论进食状态如何，脂多糖诱导的Fos表达模式在大多数下丘脑核中相似。然而，我们观察到禁食显著降低了脂多糖诱导的室旁核Fos表达，同时脂多糖诱导的厌食和体重减轻也有所减轻。此外，脂多糖降低了下丘脑外侧穹窿周区禁食诱导的Fos表达。脂多糖诱导的白细胞介素-1循环水平在不同进食状态下相似。最后，禁食而非脂多糖影响了瘦素的循环水平和弓状核中食欲相关神经肽的表达。总之，我们的数据表明，禁食通过特定下丘脑核的神经变化来调节脂多糖诱导的厌食和体重减轻。
