关键词： 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid AC BSA CRE CRE binding protein CREB EDTA ELISA FK HEPES IRS1 JAK2 JNK Janus kinase 2 MBIA NDS Ob-Rb PMSF SDS SOCS3 SRIF SRIF receptor subtype STAT3 TBS TTBS Tris-buffered saline Tris–Tween-buffered saline adenylyl cyclase bovine serum albumin c-Jun N-terminal kinase cyclic AMP response element enzyme-linked immunosorbent assay ethylenediaminetetraacetic acid forskolin frontoparietal cortex hippocampus icv insulin receptor substrate 1 insulin signaling intracerebroventricular leptin long-form of leptin receptor multiplexed bead immunoassay normal donkey serum p phenylmethylsulfonyl fluoride phosphorylated signal transducer and activator of transcription 3 sodium dodecyl sulfate somatostatin somatostatin receptors sst suppressor of cytokine signaling 3

Mesh ： Animals Blotting, Western Brain / drug effects metabolism Enzyme-Linked Immunosorbent Assay Immunoassay Injections, Intraventricular Insulin / metabolism Leptin / administration & dosage metabolism Male Rats Rats, Wistar Real-Time Polymerase Chain Reaction Receptors, Somatostatin / biosynthesis Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects physiology Somatostatin / metabolism Up-Regulation

来  源：   DOI：10.1016/j.neuroscience.2013.08.019   PDF(Sci-hub)

Abstract：
Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 μg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain.
摘要：
瘦素和生长抑素（SRIF）对食物寻求和摄取行为具有相反的作用，部分由额顶皮质和海马调节。尽管已知由瘦素介导的对食物摄入的急性抑制随着时间的推移而减少，反监管机制仍不清楚。我们的目的是分析急性中枢瘦素输注对这些区域SRIF受体效应系统的影响以及相关细胞内信号传导机制在该反应中的意义。我们研究了20只成年雄性Wister大鼠，包括对照组和单剂量5μg瘦素脑室处理的大鼠，并在1或6小时后处死。SRIF受体的密度在1h时没有变化，而瘦素在6h增加SRIF受体的密度，这与SRIF抑制两个地区毛喉素刺激的腺苷酸环化酶活性的能力升高有关。SRIF受体的功能能力没有改变，因为G抑制蛋白的αi1和αi2亚基的细胞膜水平在两个大脑区域均不受影响。SRIF受体密度的增加是由于SRIF受体亚型2(sst2)蛋白水平的增强,其与该受体的较高mRNA水平相关。这些sst2mRNA水平的变化伴随着胰岛素信号激活的增加，c-Jun和环AMP反应元件结合蛋白(CREB)；然而，信号转导和转录激活因子3的激活在皮质中减少，在海马中保持不变，细胞因子信号抑制因子3在这些区域保持不变。此外,瘦素拮抗剂L39A/D40A/F41A阻断了瘦素诱导的SRIF受体变化，瘦素信号和CREB激活。总之,瘦素输注后胰岛素信号激活的增加与SRIF受体效应系统的急性上调有关,该系统可能拮抗大鼠脑中的短期瘦素作用.
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