Retinol saturase coordinates liver metabolism by regulating ChREBP activity.
Retinol saturase coordinates liver metabolism by regulating ChREBP activity.
复制标题
视黄醇饱和度酶通过调节Chrebp活性来协调肝代谢。
DOI：
10.1038/s41467-017-00430-w
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发表时间：
2017-08-30
影响因子：
16.6
通讯作者：
Schupp M
中科院分区：
文献类型：
--
作者：
Heidenreich S;Witte N;Weber P;Goehring I;Tolkachov A;von Loeffelholz C;Döcke S;Bauer M;Stockmann M;Pfeiffer AFH;Birkenfeld AL;Pietzke M;Kempa S;Muenzner M;Schupp M
肝脏整合了多种代谢途径，保证了全身能量的动态平衡。由于慢性饮食刺激而导致的过多的造脂流量会导致肝脏脂肪变性、血脂异常和高血糖。在此，我们发现氧化还原酶视黄醇饱和酶(RetSat)参与脂肪肝的发生发展。在人类中，肝脏RetSat表达与脂肪变性和血清甘油三酯(TGS)相关。在饮食肥胖小鼠中，肝脏特异性消耗RetSat可降低肝脏和循环中的TGS，并使高血糖正常化。从机制上讲，RetSat的耗尽降低了碳水化合物反应元件结合蛋白(ChREBP)的活性，ChREBP是细胞内的己糖-磷酸感受器和脂肪生成的诱导者。RetSat耗竭时的缺陷可以通过异位表达ChREBP而不是其假定的酶产物13，14-二氢视黄醇来修复，这表明RetSat影响肝脏的葡萄糖感觉，而不是视黄醇转换。因此，RetSat是ChREBP上游肝脏代谢功能的关键调节因子。药物抑制肝脏RetSat可能是治疗脂肪变性的一种方法。脂肪肝是代谢综合征的主要特征之一，其发生与全身性脂、糖平衡紊乱有关。在这里，海登瑞克等人。表明视黄醇饱和酶通过调节转录因子ChREBP的活性参与肝脏的脂质代谢。
The liver integrates multiple metabolic pathways to warrant systemic energy homeostasis. An excessive lipogenic flux due to chronic dietary stimulation contributes to the development of hepatic steatosis, dyslipidemia and hyperglycemia. Here we show that the oxidoreductase retinol saturase (RetSat) is involved in the development of fatty liver. Hepatic RetSat expression correlates with steatosis and serum triglycerides (TGs) in humans. Liver-specific depletion of RetSat in dietary obese mice lowers hepatic and circulating TGs and normalizes hyperglycemia. Mechanistically, RetSat depletion reduces the activity of carbohydrate response element binding protein (ChREBP), a cellular hexose-phosphate sensor and inducer of lipogenesis. Defects upon RetSat depletion are rescued by ectopic expression of ChREBP but not by its putative enzymatic product 13,14-dihydroretinol, suggesting that RetSat affects hepatic glucose sensing independent of retinol conversion. Thus, RetSat is a critical regulator of liver metabolism functioning upstream of ChREBP. Pharmacological inhibition of liver RetSat may represent a therapeutic approach for steatosis. Fatty liver is one of the major features of metabolic syndrome and its development is associated with deregulation of systemic lipid and glucose homeostasis. Here Heidenreich et al. show that retinol saturase is implicated in hepatic lipid metabolism by regulating the activity of the transcription factor ChREBP.
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DOI：
10.1186/1745-7580-4-5
发表时间：
2008-04-29
期刊：
Immunome research
影响因子：
--
作者：
Lattin JE;Schroder K;Su AI;Walker JR;Zhang J;Wiltshire T;Saijo K;Glass CK;Hume DA;Kellie S;Sweet MJ
通讯作者：
Sweet MJ
DOI：
10.1073/pnas.0401516101
发表时间：
2004-05-11
影响因子：
11.1
作者：
Iizuka, K;Bruick, RK;Uyeda, K
通讯作者：
Uyeda, K
影响因子：
4.8
作者：
Cha, Ji-Young;Repa, Joyce J.
通讯作者：
Repa, Joyce J.
影响因子：
4.8
作者：
Erion, Derek M.;Popov, Violetta;Samuel, Varman T.
通讯作者：
Samuel, Varman T.
DOI：
10.1073/pnas.231370798
发表时间：
2001-11-20
影响因子：
11.1
作者：
Kawaguchi, T;Takenoshita, M;Uyeda, K
通讯作者：
Uyeda, K