The blood-brain barrier as a regulatory interface in the gut-brain axes
The blood-brain barrier as a regulatory interface in the gut-brain axes
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DOI：
10.1016/j.physbeh.2006.07.004
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发表时间：
2006-11-30
影响因子：
2.9
通讯作者：
Banks, William A.
中科院分区：
文献类型：
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作者：
Banks, William A.
血脑屏障（BBB）阻止肽和蛋白质在脑和血液之间的不受限制的运动。然而，一些肽和调节蛋白可以通过饱和和非饱和机制穿过BBB。瘦素和胰岛素各自通过其自身的转运蛋白穿过血脑屏障。瘦素转运受损发生在肥胖症中，并导致外周阻力;也就是说，当瘦素直接进入大脑时，肥胖动物体重减轻，但当外周给予瘦素时体重却没有减轻。瘦素运输也被抑制在饥饿和高脂血症。由于高胆固醇血症发生在饥饿和肥胖，我们推测，外周阻力高胆固醇血症诱导的可能已经演变为一种适应机制，在响应饥饿。胰岛素转运也受到调节。例如，用脂多糖（LPS）治疗小鼠使胰岛素通过BBB的转运增加约三倍。由于CNS胰岛素的许多作用与外周胰岛素的作用相反，并且由于LPS释放促炎细胞因子，因此胰岛素通过BBB的转运增强可能是脓毒症中促进胰岛素抵抗的机制。构成血脑屏障的脑内皮细胞分泌包括细胞因子在内的多种物质。这种分泌可以从BBB的一侧刺激并释放到另一侧。例如，脂联素似乎可以抑制脑内皮细胞释放白细胞介素-6。总的来说，血脑屏障代表了一个重要的接口，在调解肠-脑轴。(c)2006年爱思唯尔公司All rights reserved.
The blood-brain barrier (BBB) prevents the unrestricted movement of peptides and proteins between the brain and blood. However, some peptides and regulatory proteins can cross the BBB by saturable and non-saturable mechanisms. Leptin and insulin each cross the BBB by their own transporters. Impaired transport of leptin occurs in obesity and accounts for peripheral resistance; that is, the condition wherein an obese animal loses weight when given leptin directly into the brain but not when given leptin peripherally. Leptin transport is also inhibited in starvation and by hypertriglyceridemia. Since hypertriglyceridemia occurs in both starvation and obesity, we have postulated that the peripheral resistance induced by hypertriglyceridemia may have evolved as an adaptive mechanism in response to starvation. Insulin transport is also regulated. For example, treatment of mice with lipopolysaccharide (LPS) increases insulin transport across the BBB by about threefold. Since many of the actions of CNS insulin oppose those of peripheral insulin and since LPS releases proinflammatory cytokines, enhanced transport of insulin across the BBB could be a mechanism which promotes insulin resistance in sepsis. The brain endothelial cells which comprise the BBB secrete many substances including cytokines. Such secretion can be stimulated from one side of the BBB with release into the other side. For example, it appears that adiponectin can inhibit release of interleukin-6 from brain endothelial cells. Overall, the BBB represents an important interface in mediating gut-brain axes. (c) 2006 Elsevier Inc. All rights reserved.