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N-硬脂酰乙醇胺可恢复肥胖诱导的胰岛素抵抗大鼠的胰腺脂质组成。

N-stearoylethanolamine restores pancreas lipid composition in obesity-induced insulin resistant rats.

作者信息

Onopchenko Oleksandra V, Kosiakova Galina V, Oz Murat, Klimashevsky Vitaliy M, Gula Nadiya M

机构信息

Department of Biochemistry of Lipids, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine (NASU), 9 Leontovicha Street, Kyiv, 01601, Ukraine,

出版信息

Lipids. 2015 Jan;50(1):13-21. doi: 10.1007/s11745-014-3960-1. Epub 2014 Oct 15.

Abstract

This study investigates the protective effect of N-stearoylethanolamine (NSE), a bioactive N-acylethanolamine , on the lipid profile distribution in the pancreas of obesity-induced insulin resistant (IR) rats fed with prolonged high fat diet (58% of fat for 6 months). The phospholipid composition was determined using 2D thin-layer chromatography. The level of individual phospholipids was estimated by measuring inorganic phosphorus content. The fatty acid (FA) composition and cholesterol level were investigated by gas-liquid chromatography. Compared to controls, plasma levels of triglycerides and insulin were significantly increased in IR rats. The pancreas lipid composition indicated a significant reduction of the free cholesterol level and some phospholipids such as phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer) compared to controls. Moreover, the FA composition of pancreas showed a significant redistribution of the main FA (18:1n-9, 18:2n-6, 18:3n-6 and 20:4n-6) levels between phospholipid, free FA, triglyceride fractions under IR conditions that was accompanied by a change in the estimated activities of Δ9-, Δ6-, Δ5-desaturase. Administration of N-stearoylethanolamine (NSE, 50 mg/kg daily per os for 2 weeks) IR rats triggered an increase in the content of free cholesterol, PtdCho and normalization of PtdEtn, PtdSer level. Furthermore, the NSE modulated the activity of desaturases, thus influenced FA composition and restored the FA ratios in the lipid fractions. These NSE-induced changes were associated with a normalization of plasma triglyceride content, considerable decrease of insulin and index HOMA-IR level in rats under IR conditions.

摘要

本研究调查了生物活性N-酰基乙醇胺N-硬脂酰乙醇胺(NSE)对长期高脂饮食(脂肪含量58%,持续6个月)诱导的肥胖胰岛素抵抗(IR)大鼠胰腺脂质分布的保护作用。使用二维薄层色谱法测定磷脂组成。通过测量无机磷含量估算单个磷脂的水平。采用气液色谱法研究脂肪酸(FA)组成和胆固醇水平。与对照组相比,IR大鼠血浆甘油三酯和胰岛素水平显著升高。胰腺脂质组成表明,与对照组相比,游离胆固醇水平以及一些磷脂如磷脂酰胆碱(PtdCho)、磷脂酰乙醇胺(PtdEtn)、磷脂酰肌醇(PtdIns)、磷脂酰丝氨酸(PtdSer)显著降低。此外,胰腺的FA组成显示,在IR条件下,磷脂、游离FA、甘油三酯组分之间主要FA(18:1n-9、18:2n-6、18:3n-6和20:4n-6)水平发生了显著重新分布,同时伴随着Δ9-、Δ6-、Δ5-去饱和酶估计活性的变化。给IR大鼠口服N-硬脂酰乙醇胺(NSE,每天50 mg/kg,持续2周)后,游离胆固醇、PtdCho含量增加,PtdEtn、PtdSer水平恢复正常。此外,NSE调节了去饱和酶的活性,从而影响了FA组成并恢复了脂质组分中的FA比例。这些由NSE诱导的变化与IR条件下大鼠血浆甘油三酯含量正常化、胰岛素显著降低以及HOMA-IR水平降低有关。

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