Lipopolysaccharide induces adipose differentiation-related protein expression and lipid accumulation in the liver through inhibition of fatty acid oxidation in mice
Lipopolysaccharide induces adipose differentiation-related protein expression and lipid accumulation in the liver through inhibition of fatty acid oxidation in mice
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DOI：
10.1007/s00535-007-2119-8
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发表时间：
2007-12-01
影响因子：
6.3
通讯作者：
Okumura, Toshikatsu
中科院分区：
文献类型：
--
作者：
Ohhira, Masumi;Motomura, Wataru;Okumura, Toshikatsu
背景资料。在本研究中，我们研究了脂多糖(LPS)对小鼠肝脏组织病理学的影响，特别是对脂类代谢的影响。方法：研究方法。给小鼠腹腔注射脂多糖，从病理和生化角度观察其对肝脏的影响。结果。油红O染色和脂肪分化相关蛋白(Adrp)免疫组织化学结果显示，注射脂多糖可诱导肝细胞内脂质沉积和adrp的表达，尤其是门静脉周围。光镜观察发现，内毒素注射后12h，脂肪开始积聚。时程研究表明，内毒素在2小时内迅速降低肝脏核激素受体的表达，包括过氧化物酶体增殖物激活受体(PPAR)α。脂多糖抑制参与肝脏脂肪酸氧化的PPARα靶基因的表达，如编码enoyl-CoA水合酶、酰基辅酶A脱氢酶和肉碱棕榈酰转移酶-1的基因，而脂多糖也抑制与脂肪酸合成相关的基因的表达，如脂肪酸合成酶、硬脂酰辅酶A去饱和酶和乙酰辅酶A羧基酶α。结论。脂多糖通过下调PPARα相关的转录机制，抑制脂肪酸氧化，诱导肝脏一过性脂肪堆积和ADRP的表达。
Background. In the present study, we examined the effect of lipopolysaccharide (LPS) on liver histopathology with special reference to lipid metabolism in mice. Methods. Mice were injected with LPS intraperitoneally, and its effect on the liver was investigated pathologically and biochemically. Results. Oil-red O staining and adipose differentiation-related protein (ADRP) immunohistochemistry demonstrated that injection of LPS transiently induced lipid accumulation and ADRP expression in hepatocytes, especially around the portal vein. Microscopic observation revealed that lipid accumulation started 12h after LPS injection. Time-course studies showed that LPS rapidly, within 2h, decreased hepatic expression of nuclear hormone receptors, including peroxisome proliferator-activated receptor (PPAR) alpha. LPS inhibited the expression of PPAR alpha-target genes involved in fatty acid oxidation in the liver such as those coding for enoyl-CoA hydratase, acyl-CoA dehydrogenase, and carnitine palmitoyl transferase-1, whereas LPS also suppressed the expression of genes related to fatty acid synthesis such as those for fatty acid synthase, stearoyl-CoA desaturase, and acetyl-CoA carboxylase alpha. Conclusions. LPS induces transient lipid accumulation and expression of ADRP in the liver through inhibition of fatty acid oxidation by downregulation of the PPAR alpha-related transcriptional mechanism.