Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
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DOI：
10.1080/21623945.2018.1474669
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发表时间：
2018-07
期刊：
影响因子：
3.3
通讯作者：
Liang Xu;N. Nagata;Tsuguhito Ota
中科院分区：
文献类型：
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作者：
Liang Xu;N. Nagata;Tsuguhito Ota
摘要肥胖是一种低度持续性炎症状态，引起不同代谢组织的氧化应激，导致胰岛素抵抗和非酒精性脂肪性肝病(NAFLD)。尤其是肥胖诱导的代谢性内毒素血症在胰岛素抵抗和炎症的发病机制中起着重要作用。核因子红系2相关因子2(Nrf2)是抗氧化信号的关键调节因子，是抵抗氧化应激细胞毒性效应的主要细胞防御因子。Nrf2的药理刺激可以减轻小鼠的肥胖和胰岛素抵抗；然而，出于生物安全方面的考虑，Nrf2激活剂不能在临床上使用。最近的一项研究表明，萝卜素是Nrf2激活剂萝卜硫素的前体，通过增加能量消耗和白色脂肪组织的褐化来改善肥胖，并通过极化M2巨噬细胞和减少代谢性内毒素血症来减轻肥胖相关的炎症和胰岛素抵抗。因此，这篇综述主要集中在葡萄糖胺在减轻肥胖、胰岛素抵抗和NAFLD方面的有效性和安全性。缩写：ALT，丙氨酸氨基转移酶；AMPK，AMP激活的蛋白激酶；ATM，脂肪组织巨噬细胞；BAT，棕色脂肪组织；CDO-Im，2-氰基-3，12-二氧杂环烯-1，9-二烯-28-酸-咪唑烷；CDO-Me，CDDO-甲酯；DIO，高脂饮食诱导的肥胖；游离脂肪酸；成纤维细胞生长因子；GTP，谷氨酰转肽酶；HFD，高脂饮食；IKKβ，κB-激酶抑制物；IL，IL；JNK，C-Jun-末端激酶；KD，击倒；Keap1，凯氏样ECH相关蛋白1；KO，基因敲除；脂多糖；NADPH，烟酰胺腺嘌呤二核苷酸磷酸；NAFLD，非酒精性脂肪性肝病；NF-κB，核因子-κB；NRF2，核因子E2相关因子2；ROS，活性氧；T2D，2型糖尿病；TLR，Toll样受体；肿瘤坏死因子；UCP，解偶联蛋白；Wat，白色脂肪组织。
ABSTRACT Obesity is a low-grade sustained inflammatory state that causes oxidative stress in different metabolic tissues, which leads to insulin resistance and nonalcoholic fatty liver disease (NAFLD). Particularly, obesity-induced metabolic endotoxemia plays an important role in the pathogenesis of insulin resistance and inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of antioxidant signaling that serves as a primary cellular defense against the cytotoxic effects of oxidative stress. Pharmacological stimulation of Nrf2 mitigates obesity and insulin resistance in mice; however, Nrf2 activators are not clinically available due to biosafety concerns. A recent study demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia. Thus, this review focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD. Abbreviations: ALT, Alanine aminotransferase; AMPK, AMP-activated protein kinase; ATMs, Adipose tissue macrophages; BAT, Brown adipose tissue; CDDO-Im, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid-imidazolide; CDDO-Me, CDDO-methyl ester; DIO, High-fat-diet-induced obese; FFA, Free fatty acid; FGF, Fibroblast growth factor; GTP, Glutamyl transpeptidase; HFD, High-fat diet; IKKβ, Inhibitor of κB-kinase β; IL, Interleukin; JNK, C-Jun N-terminal kinase; KD, Knockdown; Keap1, Kelch-like ECH-associated protein 1; KO, Knockout; LPS, Lipopolysaccharide; NADPH, Nicotinamide adenine dinucleotide phosphate; NAFLD, Non-alcoholic fatty liver disease; NF-κB, Nuclear factor-κB; Nrf2, Nuclear factor E2-related factor 2; ROS, Reactive oxygen species; T2D, Type 2 diabetes; TLR, Toll-like receptor; TNF, tumor necrosis factor; UCP, Uncoupling protein; WAT, White adipose tissue.