过氧化物酶体增殖物激活受体α、γ调控长链酰基辅酶A合成酶1对肝纤维化进程的影响

辛萱; 颜红柱; 李维卿; 余宏宇

doi:10.3969/j.issn.1001-5256.2014.07.034

过氧化物酶体增殖物激活受体α、γ调控长链酰基辅酶A合成酶1对肝纤维化进程的影响

DOI: 10.3969/j.issn.1001-5256.2014.07.034

1. 第二军医大学长征医院病理科
2. 济南军区总医院病理科

详细信息

中图分类号: R575.2
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出版历程
- 收稿日期: 2013-09-09
- 出版日期: 2014-07-20

Studies on PPAR α and γ participating in progression of liver fibrosis by regulating ACSL1

Department of Pathology, Changzheng Hospital, Second Military Medical University

摘要

摘要: 在肝纤维化的发生发展进程中,过氧化物酶体增殖物激活受体(PPAR)α、γ具有调控脂代谢、脂肪酸代谢和抗肝纤维化等生物学功能,并与调控脂肪代谢的相关酶类关系密切。长链酰基辅酶A合成酶1(ACSL1)作为脂肪代谢的关键酶之一,在肝脏中参与脂质的合成与分解代谢,可引起肝脏内脂质沉积、炎症反应,并在肝脏中直接或间接促进肝纤维化进程。回顾了PPARα、γ和ACSL1各自的生物学功能与作用;简述了PPARα、γ对ACSL1的转录调控机制;从肝脏脂代谢和肝星状细胞活化等两个方面分析了PPARα、γ对ACSL1的调控作用,进而影响肝纤维化进程。从而指出在肝脏中PPARα、γ通过调控ACSL1直接或间接参与肝纤维化进程。
- PPARα /
- PPARγ /
- 酰基辅酶A /
- 肝硬化 /
- 综述
Abstract: During the development and procession of liver fibrosis, peroxisome proliferator- activated receptor (PPAR) α and γ are in charge of the regulation of lipid metabolism, fatty acid metabolism, anti- liver fibrosis, etc., and are closely related to fat metabolism- related enzymes. As a key enzyme in fat metabolism, acyl- CoA synthetase long- chain family member 1 (ACSL1) is involved in lipid synthesis and catabolism and then causes lipid deposition and inflammation in the liver, so it directly or indirectly promotes hepatic fibrosis. The biological functions and roles of PPAR α and γ and ACSL1 are reviewed; the action mechanisms of PPAR α and γ in the transcriptional regulation of ACSL1 are briefly described; the regulatory effects of PPAR α and γ on ACSL1 and their effects on the progression of hepatic fibrosis are analyzed from the aspects of liver lipid metabolism and hepatic stellate cell activation. It is pointed out that in the liver PPAR α andγ are directly or indirectly involved in the progression of hepatic fibrosis by regulating ACSL1.
- PPAR alpha /
- PPAR gamma /
- acyl coenzyme A /
- liver cirrhosis /
- review

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参考文献(19)

[1]GONZALEZ FJ, SHAH YM.PPAR alpha:mechanism of species differences and hepatocarcino genesis of peroxisome proliferators[J].Toxicology, 2008, 246 (1) :2-8.

[2]FILIP-CIUBOTARU F, FOIA L, MANCIUC C, et al.PPARs:structure, mechanisms of action and control.NoteI[J].Rev Med Chir Soc Med Nat Iasi, 2011, 115 (2) :477-484.

[3]MANDRUP S, LANE MD.Regulating adipogenesis[J].J Biol Chem, 1997, 272:5367-5370.

[4]MARCUS SL, MIYATA KS, ZHANG BW, et al.Diverse peroxisome proliferator-activated receptors bind to the peroxisome proliferatorresponsive elements of the rat hydratase/de-hydroganase and fatty acyl-CoA oxidase genes but diferentially induce expression[J].Proc Natl Acad Sci U S A, 1993, 90 (12) :5723-5727.

[5]DREYER C, KREY G, KELLER H, et al.Control of the peroxisomeβoxidation pathway by a novel family of nuclear hormone receptors[J].Cell, 1992, 68 (5) :879-887.

[6]BERGER J, MOLLER DE.The mechanisms of action of PPARs[J].Annu Rev Med, 2002, 53:409-435.

[7]REDDY RC.Immunomodulatory role of PPAR-gamma in alveolar macrophages[J].J Investig Med, 2008, 56 (2) :522-527.

[8]GHOSH AK, WEI J, WU MH, et al.Constitutive Smad signaling and Smad-dependent collagen gene expression in mouse embryonic fibroblasts lacking peroxisome proliferator activated receptor-gamma[J].Biochem Biophys Res Commun, 2008, 374 (2) :231-236.

[9]SOUPENE E, KUYPERS FA.Mammalian long-chain acyl-CoA synthetases[J].Exp Biol Med (Maywood) , 2008, 233 (5) :507-521.

[10]LI LO, KLETT L, COLEMAN RA.Acyl-CoA synthesis, lipid metabolism and lipotoxicity[J].Biochim Biophys Acta, 2010, 1801 (3) :246-251.

[11]LI LO, MASHEK DG, AN J, et al.Overexpression of rat long chain acyl-CoA synthetase 1 alters fatty acid metabolism in rat primary hepatocytes[J].J Biol Chem, 2006, 281 (48) :37246-37255.

[12]MUOIO DM, LEWIN TM, WIEDMER P, et al.Acyl-CoAs are functionally channeled in liver:potential role of acyl-CoA synthetase[J].Am J Physiol Endocrinol Metab, 2000, 279 (6) :1366-1373.

[13]FU M, ZHANG J, LIN Y, et al.Eady growth response factor-1 is a critical transcriptional mediator of peroxisome proliferator-activated receptor-γ/1 gene expression in human aortic smooth muscle cells[J].J Biol Chem, 2002, 277 (30) :26808-26814.

[14]IP E, FARRELL GC, ROBERTSO G, et al.Central role of PPAR alpha dependent hepatic lipid turnover in dietary steatohepatitis in mice[J].Hepatology, 2003, 38 (1) :123-132.

[15]REDDY JZ.Nonalcoholic steatosis and steatohepatitis.Ⅲ.Pemxisomal beta-oxidation, PPAR alpha, and steatohepatitis[J].Am J Physiol Gastmintest Liver Physiol, 2001, 281 (6) :1333-1339.

[16]CARPINO G, MORIN S, GINANNI CORRADINI S, et al.Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurent chronic hepatitis after liver transplantation[J].Dig Liver Dis, 2005, 37 (5) :349-356.

[17]UTO H, NAKANISHI L, IDO A, et al.The peroxisome proliferator-activated receptor-gamma agonist, pioglitazone, inhibits fat accumulation and fibrosis in the livers of rats fed a choline-deficient, l-amino acid-defined diet[J].Hepatol Res, 2005, 32 (4) :235-242.

[18]LI LO, ELLIS M, HEATHER A, et al.Liver-specific loss of long chain acyl-CoA synthetase-1 decreases triacylglycerol synthesis andβ-Oxidation and alters phospholipid fatty acid composition[J].J Biol Chem, 2009, 284 (41) :27816-27826.

[19]LU LG, LI ZH.Recent research on liver fibrosis and cirrhosis[J].J Clin Hepatol, 2013, 29 (5) :321-323. (in Chinese) 陆伦根, 李郑红.肝纤维化及肝硬化近况研究[J].临床肝胆病杂志, 2013, 29 (5) :321-323.

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