Roles of IκB kinases and TANK-binding kinase 1 in hepatic lipid metabolism and nonalcoholic fatty liver disease.
Roles of IκB kinases and TANK-binding kinase 1 in hepatic lipid metabolism and nonalcoholic fatty liver disease.
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DOI：
10.1038/s12276-021-00712-w
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发表时间：
2021-11
影响因子：
12.8
通讯作者：
Saltiel AR
中科院分区：
文献类型：
--
作者：
Huh JY;Saltiel AR
非酒精性脂肪性肝病（NAFLD）是慢性肝病最常见的原因，与肥胖相关的肝脏异位脂肪堆积密切相关。肝脏脂质蓄积包括从单纯性脂肪变性到非酒精性脂肪性肝炎（NASH）的组织学谱，NASH可进展为肝硬化和肝细胞癌。鉴于肝脏脂质代谢失调可能是NAFLD的发病因素，了解健康受试者中肝脏脂质代谢如何调节以及NAFLD受试者中哪些步骤失调对于确定有效的治疗靶点至关重要。此外，肝脏炎症参与NAFLD进展期间的慢性肝细胞损伤。IκB激酶（IKK）复合物（包括IKKα、IKKβ和IKKγ（NEMO））作为介导NF-κB活化的关键免疫信号传导枢纽，已被研究为肝脏炎症反应和肝细胞存活的关键调节剂。值得注意的是，TANK结合激酶1（TBK 1），一种IKK相关激酶，最近被发现是肝脏炎症和能量代谢之间的潜在联系。在此，我们综述（1）肝脏脂质代谢的生化步骤;（2）肥胖和NAFLD中脂质代谢失调;（3）IKK和TBK 1在肥胖和NAFLD中的作用。深入了解非酒精性脂肪性肝病（NAFLD）中脂肪酸代谢功能障碍的分子过程有助于保护患者免受严重肝损伤。NAFLD是肥胖的常见后果，严重的疾病最终可能导致肝癌或肝硬化。美国圣地亚哥加州大学的Alan Saltiel和韩国首尔国立大学的Jin Young Huh回顾了目前对肝脏脂肪酸代谢机制的认识，以及它们在肥胖和NAFLD中是如何受到干扰的。各种IκB激酶（IKK）复合物和一种称为TANK结合激酶1（TBK 1）的蛋白质在与NAFLD发病机制相关的炎症反应中起着特别重要的作用。更好地了解IKK和TBK 1相关的调节途径可以为这种目前无法治疗的疾病提供新的干预措施。
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is strongly associated with obesity-related ectopic fat accumulation in the liver. Hepatic lipid accumulation encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Given that dysregulated hepatic lipid metabolism may be an onset factor in NAFLD, understanding how hepatic lipid metabolism is modulated in healthy subjects and which steps are dysregulated in NAFLD subjects is crucial to identify effective therapeutic targets. Additionally, hepatic inflammation is involved in chronic hepatocyte damage during NAFLD progression. As a key immune signaling hub that mediates NF-κB activation, the IκB kinase (IKK) complex, including IKKα, IKKβ, and IKKγ (NEMO), has been studied as a crucial regulator of the hepatic inflammatory response and hepatocyte survival. Notably, TANK-binding kinase 1 (TBK1), an IKK-related kinase, has recently been revealed as a potential link between hepatic inflammation and energy metabolism. Here, we review (1) the biochemical steps of hepatic lipid metabolism; (2) dysregulated lipid metabolism in obesity and NAFLD; and (3) the roles of IKKs and TBK1 in obesity and NAFLD. A deeper understanding of the molecular processes underlying dysfunctional fatty-acid metabolism in nonalcoholic fatty liver disease (NAFLD) could help protect patients from severe liver damage. NAFLD is a common consequence of obesity, and severe disease can ultimately give rise to liver cancer or cirrhosis. Alan Saltiel of the University of California, San Diego, USA, and Jin Young Huh of Seoul National University, South Korea, have reviewed current knowledge of the mechanisms governing fatty acid metabolism in the liver, and how they are disturbed in obesity and NAFLD. The various IκB kinase (IKK) complexes and a protein known as TANK-binding kinase 1 (TBK1) play particularly prominent roles in the inflammatory response associated with NAFLD pathogenesis. Better insights into IKK- and TBK1-associated regulatory pathways could inform the development of new interventions for this currently untreatable condition.
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影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
5.2
作者：
Choe SS;Huh JY;Hwang IJ;Kim JI;Kim JB
通讯作者：
Kim JB
DOI：
10.1073/pnas.0931394100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Chirala, SS;Chang, H;Wakil, SJ
通讯作者：
Wakil, SJ
影响因子：
11.4
作者：
Bonnard, M;Mirtsos, C;Yeh, WC
通讯作者：
Yeh, WC
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH