Central Adiponectin Acutely Improves Glucose Tolerance in Male Mice
Central Adiponectin Acutely Improves Glucose Tolerance in Male Mice
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DOI：
10.1210/en.2013-1734
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发表时间：
2014-05-01
期刊：
影响因子：
4.8
通讯作者：
Tups, Alexander
中科院分区：
文献类型：
--
作者：
Koch, Christiane E.;Lowe, Chrishanthi;Tups, Alexander
脂联素是一种脂肪细胞来源的激素，调节葡萄糖和脂质代谢。也是。在肥胖期间，脂联素水平和敏感性降低。虽然脂联素在外周的作用已得到充分证实，但脂联素的神经内分泌作用在很大程度上尚不清楚。为了解决这一问题，我们分析了脂联素和2种脂联素受体（AdipoR 1和AdipoR 2）在禁食和饮食诱导的遗传性肥胖中的表达。我们还研究了脂联素对葡萄糖稳态中枢调节的急性影响。脑室内（ICV）注射脂联素（1 μ g），并在饮食和遗传性肥胖小鼠中进行葡萄糖耐量试验。最后，评估ICV脂联素给药对调节葡萄糖稳态的中枢信号级联和下丘脑炎症标志物的影响。在禁食小鼠的弓状核中，脂联素的基因表达下调，而AdipoR 1的基因表达上调。高脂（HF）喂养增加了该区域的AdipoR 1和AdipoR 2基因表达。在HF饮食的小鼠和瘦素缺乏的小鼠中，急性ICV脂联素在注射后60分钟改善了葡萄糖耐量，而对照小鼠中的normoprotein不受影响。ICV脂联素增加pAKT，降低磷酸-AMP-活化蛋白激酶，并没有改变磷酸信号转导和转录激活因子3免疫反应性。在HF喂养的小鼠中，ICV脂联素逆转了下丘脑炎症和胰岛素抵抗的参数，这些参数由弓状核和下丘脑腹内侧的磷酸糖原合成酶激酶3 β（Ser 9）和磷酸-c-Jun N-末端激酶（Thr 183/Tyr 185）免疫反应性细胞的数量确定。这项研究表明，脂联素的胰岛素增敏特性至少部分是基于神经内分泌机制，涉及中枢合成脂联素。
Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 mu g) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 beta(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin.