Department of Animal Physiology (C.E.K., C.L., K.L., J.B., A.B., G.B., A.T.), Faculty of Biology, Philipps University Marburg, D-35043 Marburg, Germany; Metabolic Health Group (L.M.W.), Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB21 9SB, United Kingdom; and Centre for Neuroendocrinology and Department of Anatomy and Structural Biology (D.R.G.), University of Otago, Dunedin, New Zealand.
Endocrinology. 2014 May;155(5):1806-16. doi: 10.1210/en.2013-1734. Epub 2014 Feb 24.
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 μg) 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 β(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.
脂联素是一种脂肪细胞来源的激素，可调节葡萄糖和脂质代谢。它还具有抗炎作用。在肥胖过程中，脂联素的水平和敏感性降低。虽然外周脂联素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，我们分析了在禁食、饮食诱导和遗传肥胖的情况下，脂联素及其 2 种受体（AdipoR1 和 AdipoR2）的表达情况。我们还研究了脂联素对中枢葡萄糖稳态调节的急性影响。向饮食和遗传肥胖的小鼠的中枢脑室（ICV）内注射 1μg 脂联素，并进行葡萄糖耐量试验。最后，评估了 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。禁食小鼠弓状核中脂联素的基因表达下调，而 AdipoR1 上调。高脂肪（HF）喂养增加了该区域的 AdipoR1 和 AdipoR2 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，而对照小鼠的正常血糖不受影响。ICV 脂联素增加了 pAKT，降低了磷酸化 AMP 激活的蛋白激酶，但不改变磷酸化信号转导和转录激活因子 3 的免疫反应性。在 HF 喂养的小鼠中，ICV 脂联素逆转了弓状核和腹内侧下丘脑磷酸化糖原合成酶激酶 3β（Ser9）和磷酸化 c-Jun N-末端激酶（Thr183/Tyr185）免疫反应性细胞数量等下丘脑炎症和胰岛素抵抗的参数。这项研究表明，脂联素的胰岛素增敏特性至少部分基于一种涉及中枢合成脂联素的神经内分泌机制。
