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Diabetes:中枢抑制IKKβ/NF-κB 信号通路可改善代谢紊乱

来源:生物谷 2015-02-04 13:45

   

2015年2月4日讯 /生物谷BIOON/ --近日,来自德国的科学家在著名国际糖尿病学期刊Diabetes上在线刊登了他们的一项最新研究成果,他们发现中枢神经系统中IKKβ/NF-κB信号途径会促进营养过剩诱导的代谢综合症以及相关的代谢紊乱如肥胖,瘦素和胰岛素抵抗以及II型糖尿病。
 
研究人员指出中枢神经系统中的代谢炎症可能是导致代谢紊乱的诱发因素。研究人员在高脂诱导的肥胖小鼠和ob/ob小鼠中抑制中枢神经系统中的IKKβ/NF-κB途径能够改善代谢损伤。通过口服,腹腔注射和脑室注射的方法,研究人员发现类黄酮能够增强血糖耐受以及下丘脑的胰岛素信号通路,并且这种剂量依赖性的血糖下降并不受瘦素缺失以及高脂饮食诱导的肥胖影响。为证明中枢神经系统中IKKβ/NF-κB信号途径在调控血糖和能量平衡方面的显著作用,研究人员通过基因修饰的方法抑制了弓状核神经元中的IKKβ/NF-κB信号途径,处理后发现高脂诱导小鼠出现体重和脂肪含量下降,能量消耗增加以及瘦素信号通路增强等代谢改善表型。
 
综上所述,该文章证明了中枢神经系统中IKKβ/NF-κB促炎症信号途径对代谢的不良影响,并且发现类黄酮可能具有改善代谢的潜在作用。这些结果表明或可针对中枢神经系统中IKKβ/NF-κB促炎症信号途径开发治疗饮食诱导肥胖及并发症的新方法。(生物谷Bioon.com)
 
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Central inhibition of IKKβ/NF-κB signalling attenuates high fat diet-induced obesity and glucose intolerance
 
Jonas Benzler1, Goutham K. Ganjam2, Dominik Pretz1,Rebecca Oelkrug1, Christiane E. Koch1, Karen Legler1, Sigrid St?hr1,Carsten Culmsee3, Lynda M. Williams4 and Alexander Tups
 
Metabolic inflammation in the central nervous system might be causative for the development of over nutrition-induced metabolic syndrome and related disorders such as obesity, leptin- and insulin-resistance and type II diabetes. Here we investigated whether nutritive and genetic inhibition of the central IKKβ/NF-κB pathway in DIO- and leptin-deficient mice improves these metabolic impairments. A known prominent inhibitor of IKKβ/NF-κB signalling is the dietary flavonoid butein. We initially determined that oral, intraperitoneal and intracerebroventricular administration of this flavonoid improved glucose tolerance and hypothalamic insulin signalling. The dose-dependent glucose lowering capacity was profound regardless of whether obesity was caused by leptin deficiency or high fat diet. To confirm the apparent central role of IKKβ/NF-κB signalling in the control of glucose- and energy homeostasis we genetically inhibited this pathway in neurons of the arcuate nucleus, one key centre for control of energy homeostasis, via specific AAV2-mediated over-expression of IκBα, which inhibits NF-κB nuclear translocation. This treatment attenuated high fat diet-induced body weight gain, body fat mass accumulation, increased energy expenditure and reduced arcuate SOCS-3 expression, indicative for enhanced leptin signalling. These results reinforce a specific role of central pro-inflammatory IKKβ/NF-κB signalling in the development and potential treatment of DIO-induced co-morbidities.
 

 

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