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非酒精性脂肪性肝病与代谢综合征相关:肝纤维化分期对极低密度脂蛋白特征的影响。

Nonalcoholic fatty liver disease associated with metabolic syndrome: Influence of liver fibrosis stages on characteristics of very low-density lipoproteins.

机构信息

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Argentina; Universidad de Buenos Aires, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Argentina; Universidad de Buenos Aires, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.

出版信息

Clin Chim Acta. 2017 Oct;473:1-8. doi: 10.1016/j.cca.2017.08.006. Epub 2017 Aug 9.

Abstract

BACKGROUND

We evaluated possible changes in VLDLcharacteristics, and metabolic related factors, in MetS-associated NAFLD and accompanying liver fibrosis.

METHODS

We studied 36 MetS patients with biopsy-proven NAFLD (MetS+NAFLD) and 24 MetS without ultrasound NAFLD evidence. Further, MetS+NAFLD was sub-divided according to fibrosis stage into, non-to-moderate (F0-F2, n=27) and severe (F3-F4, n=9) fibrosis. We measured: lipid profile, VLDL composition and size (size exclusion-HPLC), CETP and lipoprotein lipase (LPL) activities and adiponectin. Additionally, in MetS+NAFLD type IV collagen 7S domain was measured.

RESULTS

MetS+NAFLD showed increased VLDL-mass, VLDL particle number, VLDL-triglyceride% and large VLDL-% (p<0.04). CETP activity tended to increase in MetS+NAFLD (p=0.058), while LPL activity was unchanged. Moreover, in MetS+NAFLD, adiponectin was decreased (p<0.001), and negatively correlated with VLDL-mass and VLDL particle number (p<0.05), independently of insulin-resistance. Within MetS+NAFLD group, despite greater insulin-resistance, patients with severe fibrosis showed lower plasma triglycerides, VLDL-mass, VLDL-triglyceride%, large VLDL-% and CETP activity (p<0.05), while type IV collagen was increased (p=0.009) and inversely correlated with large VLDL-% (p=0.045).

CONCLUSIONS

In MetS, NAFLD is associated with larger and triglyceride over-enriched circulating VLDLs, of greater atherogenicity. However, when NAFLD progresses to severe fibrosis, circulating VLDL features apparently improved, probably due to early alterations in hepatic synthetic function.

摘要

背景

我们评估了代谢综合征相关非酒精性脂肪性肝病(NAFLD)伴发肝纤维化患者的极低密度脂蛋白(VLDL)特征及代谢相关因素可能发生的变化。

方法

我们研究了 36 名经活检证实患有非酒精性脂肪性肝病的代谢综合征患者(MetS+NAFLD)和 24 名无超声 NAFLD 证据的代谢综合征患者。此外,根据纤维化分期,MetS+NAFLD 进一步分为非严重至中度纤维化(F0-F2,n=27)和严重纤维化(F3-F4,n=9)。我们测量了血脂谱、VLDL 组成和大小(排阻高效液相色谱法)、CETP 和脂蛋白脂肪酶(LPL)活性以及脂联素。此外,在 MetS+NAFLD 中还测量了 7S 结构域 IV 型胶原。

结果

MetS+NAFLD 患者的 VLDL 质量、VLDL 颗粒数、VLDL 甘油三酯%和大 VLDL-%均增加(p<0.04)。CETP 活性在 MetS+NAFLD 中呈上升趋势(p=0.058),而 LPL 活性无变化。此外,MetS+NAFLD 患者的脂联素降低(p<0.001),与 VLDL 质量和 VLDL 颗粒数呈负相关(p<0.05),与胰岛素抵抗无关。在 MetS+NAFLD 组中,尽管胰岛素抵抗更严重,但严重纤维化患者的血浆甘油三酯、VLDL 质量、VLDL 甘油三酯%、大 VLDL-%和 CETP 活性均降低(p<0.05),而 IV 型胶原增加(p=0.009),与大 VLDL-%呈负相关(p=0.045)。

结论

在代谢综合征中,NAFLD 与更大且富含甘油三酯的循环 VLDL 相关,具有更大的动脉粥样硬化性。然而,当 NAFLD 进展为严重纤维化时,循环 VLDL 特征明显改善,可能是由于肝合成功能的早期改变。

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