Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, Republic of Korea.
PLoS One. 2011 Jan 20;6(1):e15981. doi: 10.1371/journal.pone.0015981.
BACKGROUND/OBJECTIVE: Visfatin, also known as nicotiamide phosphoribosyltransferase or pre-B cell colony enhancing factor, is a pro-inflammatory cytokine whose serum level is increased in sepsis and cancer as well as in obesity. Here we report a pro-inflammatory role of visfatin in the brain, to mediate sickness responses including anorexia, hyperthermia and hypoactivity.
Rats were intracerebroventricularly (ICV) injected with visfatin, and changes in food intake, body weight, body temperature and locomotor activity were monitored. Real-time PCR was applied to determine the expressions of pro-inflammatory cytokines, proopiomelanocortin (POMC) and prostaglandin-synthesizing enzymes in their brain. To determine the roles of cyclooxygenase (COX) and melanocortin in the visfatin action, rats were ICV-injected with visfatin with or without SHU9119, a melanocortin receptor antagonist, or indomethacin, a COX inhibitor, and their sickness behaviors were evaluated.
Administration of visfatin decreased food intake, body weight and locomotor activity and increased body temperature. Visfatin evoked significant increases in the levels of pro-inflammatory cytokines, prostaglandin-synthesizing enzymes and POMC, an anorexigenic neuropeptide. Indomethacin attenuated the effects of visfatin on hyperthermia and hypoactivity, but not anorexia. Further, SHU9119 blocked visfatin-induced anorexia but did not affect hyperthermia or hypoactivity.
Visfatin induced sickness responses via regulation of COX and the melanocortin pathway in the brain.
背景/目的：内脂素，又名烟酰胺磷酸核糖基转移酶或前 B 细胞集落增强因子，是一种促炎细胞因子，其血清水平在败血症和癌症以及肥胖症中升高。在这里，我们报告了内脂素在大脑中的促炎作用，以介导包括厌食、发热和活动减少在内的疾病反应。
通过脑室内（ICV）注射内脂素，监测大鼠的食物摄入量、体重、体温和运动活性的变化。应用实时 PCR 确定其大脑中促炎细胞因子、前阿黑皮素原（POMC）和前列腺素合成酶的表达。为了确定环加氧酶（COX）和黑素皮质素在内脂素作用中的作用，通过脑室内注射内脂素并加入黑素皮质素受体拮抗剂 SHU9119 或 COX 抑制剂吲哚美辛，评估其疾病行为。
内脂素的给药减少了食物摄入量、体重和运动活性，并增加了体温。内脂素引起促炎细胞因子、前列腺素合成酶和厌食性神经肽 POMC 水平显著增加。吲哚美辛减弱了内脂素对发热和活动减少的作用，但对厌食没有影响。此外，SHU9119 阻断了内脂素引起的厌食症，但对发热或活动减少没有影响。
内脂素通过调节大脑中的 COX 和黑素皮质素途径引起疾病反应。
