Lipidomics reveals a link between CYP1B1 and SCD1 in promoting obesity.
Lipidomics reveals a link between CYP1B1 and SCD1 in promoting obesity.
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脂质组学揭示 CYP1B1 和 SCD1 之间促进肥胖的联系
DOI：
10.1021/pr500145n
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发表时间：
2014-05-02
影响因子：
4.4
通讯作者：
Gonzalez, Frank J.
中科院分区：
文献类型：
--
作者：
Li, Fei;Jiang, Changtao;Larsen, Michele C.;Bushkofsky, Justin;Krausz, Kristopher W.;Wang, Ting;Jefcoate, Colin R.;Gonzalez, Frank J.
细胞色素P450 1B 1（CYP 1B 1）参与外源性化合物和内源性代谢物的代谢。尽管CYP 1B 1在肝细胞中的组成性表达最小，但在小鼠中Cyp 1b 1的破坏导致高脂饮食（HFD）诱导的肥胖的抑制和肝脏能量调节的广泛变化。缺乏CYP 1B 1与脂质代谢改变相关，特别是溶血磷脂酰胆碱，有助于防止肥胖。基于超高效液相色谱-电喷雾电离四极杆质谱（UPLC-ESI-QTOFMS）的代谢组学研究显示，溶血磷脂酰胆碱18：0（LPC 18：0）是与HFD诱导的肥胖呈正相关的生物标志物。野生型小鼠中增加的血清LPC 18：0在接受HFD的Cyp 1b 1基因敲除小鼠中降低，而在CYP 1B 1人源化小鼠中逆转。CYP 1B 1-人源化小鼠与Cyp 1b 1-null小鼠相比显示出更高的饮食诱导的肥胖，这表明人CYP 1B 1显示出与小鼠Cyp 1b 1相似的对HFD的反应。此外，肝硬脂酰辅酶A去饱和酶1（SCD 1）的表达减少Cyp 1b 1-null小鼠，和减少饮食诱导的肥胖和较低的血清LPC 18：0在SCD 1过表达后，增加Cyp 1b 1-null小鼠，这表明SCD 1与CYP 1B 1诱导的肥胖。这些研究建立了细胞色素P450、脂质和代谢紊乱之间的生物化学联系，并表明抑制CYP 1B 1可能是减肥药物的靶点。
Cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of xenobiotic compounds and endogenous metabolites. Disruption of Cyp1b1 in mice results in suppression of high-fat diet (HFD)-induced obesity and an extensive change in hepatic energy regulation despite minimal constitutive expression of CYP1B1 in hepatocytes. Lack of CYP1B1 is correlated with altered lipid metabolism, especially lysophosphatidylcholines, contributing to protection against obesity. Ultraperformance liquid chromatography coupled to electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOFMS)-based metabolomics revealed lysophosphatidylcholine 18:0 (LPC 18:0) as a biomarker positively related to HFD-induced obesity. The increased serum LPC 18:0 in wild-type mice is reduced in Cyp1b1-null mice on a HFD, which is reversed in CYP1B1-humanized mice. CYP1B1-humanized mice show higher diet-induced obesity compared with Cyp1b1-null mice, suggesting that human CYP1B1 shows a similar response to HFD as mouse Cyp1b1. In addition, hepatic stearoyl-CoA desaturase 1 (SCD1) expression was decreased in Cyp1b1-null mice, and the attenuated diet-induced obesity and lower serum LPC 18:0 in the Cyp1b1-null mice is elevated after SCD1 overexpression, suggesting that SCD1 is correlated with CYP1B1-induced obesity. These studies establish a biochemical link between cytochromes P450, lipids, and metabolic disorders and suggest that inhibition of CYP1B1 could be target for antiobesity drugs.
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影响因子：
3.3
作者：
De Pergola G;Silvestris F
通讯作者：
Silvestris F
影响因子：
4.8
作者：
Donovan EL;Pettine SM;Hickey MS;Hamilton KL;Miller BF
通讯作者：
Miller BF
影响因子：
4.4
作者：
Li F;Pang X;Krausz KW;Jiang C;Chen C;Cook JA;Krishna MC;Mitchell JB;Gonzalez FJ;Patterson AD
通讯作者：
Patterson AD
影响因子：
4.4
作者：
Kim, Hyun-Jin;Kim, Jin Hee;Yoon, Suk Hoo
通讯作者：
Yoon, Suk Hoo
影响因子：
15.9
作者：
Gutierrez-Juarez, Roger;Pocai, Alessandro;Rossetti, Luciano
通讯作者：
Rossetti, Luciano