Metabolic endotoxemia with obesity: Is it real and is it relevant?
Metabolic endotoxemia with obesity: Is it real and is it relevant?
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DOI：
10.1016/j.biochi.2015.06.020
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发表时间：
2016-05
期刊：
影响因子：
3.9
通讯作者：
Hulver MW
中科院分区：
文献类型：
--
作者：
Boutagy NE;McMillan RP;Frisard MI;Hulver MW
肥胖与多个组织的代谢紊乱有关，从而导致胰岛素抵抗和代谢综合征的进展。肥胖中这些代谢紊乱的潜在刺激因素尚未完全阐明，但最近在啮齿动物和人类中的证据表明，肠道源性内毒素（脂多糖，LPS）的系统性低水平升高可能在肥胖相关的全身和组织特异性代谢扰动中发挥重要作用。 LPS 启动一个特征明确的信号级联，当与其受体 Toll 样受体 4 (TLR4) 结合时，引发许多促炎和抗炎途径。血浆 LPS 的低度升高被称为“代谢性内毒素血症”，这种状态与肥胖中常见的促炎和氧化环境升高有关。鉴于炎症和氧化应激在肥胖相关心脏代谢疾病风险病因学中的作用，有人认为代谢性内毒素血症可能是肥胖中观察到的代谢紊乱的关键介质。本综述提供了与细胞和动物模型之间的机制关联的支持证据，并提供了肥胖症中代谢性内毒素血症的临床相关性的补充证据，因为它与人类炎症和代谢紊乱有关。考虑内毒素检测的差异，并建议采用报告代谢内毒素血症的替代方法，直到制定标准化测量方案。
Obesity is associated with metabolic derangements in multiple tissues, which contribute to the progression of insulin resistance and the metabolic syndrome. The underlying stimulus for these metabolic derangements in obesity are not fully elucidated, however recent evidence in rodents and humans suggests that systemic, low level elevations of gut derived endotoxin (lipopolysaccharide, LPS) may play an important role in obesity related, whole-body and tissue specific metabolic perturbations. LPS initiates a well-characterized signaling cascade that elicits many pro-and anti-inflammatory pathways when bound to its receptor, Toll-Like Receptor 4 (TLR4). Low-grade elevation in plasma LPS has been termed “metabolic endotoxemia” and this state is associated with a heightened pro-inflammatory and oxidant environment often observed in obesity. Given the role of inflammatory and oxidative stress in the etiology of obesity related cardio-metabolic disease risk, it has been suggested that metabolic endotoxemia may serve a key mediator of metabolic derangements observed in obesity. This review provides supporting evidence of mechanistic associations with cell and animal models, and provides complimentary evidence of the clinical relevance of metabolic endotoxemia in obesity as it relates to inflammation and metabolic derangements in humans. Discrepancies with endotoxin detection are considered, and an alternate method of reporting metabolic endotoxemia is recommended until a standardized measurement protocol is set forth.