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反式棕榈油酸对肝细胞活力、沉默调节蛋白1基因表达及过氧化物酶体增殖物激活受体α活性的影响

The effect of trans-palmitoleic acid on cell viability and sirtuin 1 gene expression in hepatocytes and the activity of peroxisome-proliferator-activated receptor-alpha.

作者信息

Farokh Nezhad Ramesh, Nourbakhsh Mitra, Razzaghy-Azar Maryam, Sharifi Roya, Yaghmaei Parichehreh

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

J Res Med Sci. 2020 Nov 26;25:105. doi: 10.4103/jrms.JRMS_16_20. eCollection 2020.

Abstract

BACKGROUND

Accumulation of fatty acids in liver causes lipotoxicity which is followed by nonalcoholic fatty liver disease. The association between intakes of trans-fatty acids with metabolic diseases is still controversial. Accordingly, the objective of this study was to investigate the effects of trans-palmitoleic acid (tPA) and palmitic acid (PA) on lipid accumulation in hepatocytes, focusing on the gene expression of sirtuin 1 (SIRT1) as well as the transcriptional activity of peroxisome proliferator-activated receptor alpha (PPARα).

MATERIALS AND METHODS

In this experimental study, hepatocellular carcinoma (HepG2) cells were cultured and treated with various concentrations of tPA and PA (C16:0). The accumulation of triglyceride in the cells was measured by enzymatic method. Gene expression was evaluated by real-time polymerase chain reaction. The activity of PPARα was assessed by luciferase reporter assay after transfection of human embryonic kidney 293T cells by a vector containing the PPAR response element.

RESULTS

While concentration >1 mM for PA and cis-PA (cPA) reduced the viability of hepatocytes, tPA revealed an opposite effect and increased cell survival. Lipid accumulation in HepG2 cells after treatment with tPA was significantly lower than that in cells treated with PA. In addition, tPA at physiological concentration had no effect on the expression of SIRT1 while at high concentration significantly augmented its expression. There was a modest increase in PPARα activity at low concentration of tPA.

CONCLUSION

tPA causes less lipid accumulation in hepatocytes with no detrimental effect on cell viability and might be beneficial for liver cells by the activation of SIRT1 and induction of PPARα activity.

摘要

背景

肝脏中脂肪酸的积累会导致脂毒性,进而引发非酒精性脂肪性肝病。反式脂肪酸摄入量与代谢性疾病之间的关联仍存在争议。因此,本研究的目的是研究反式棕榈油酸(tPA)和棕榈酸(PA)对肝细胞脂质积累的影响,重点关注沉默调节蛋白1(SIRT1)的基因表达以及过氧化物酶体增殖物激活受体α(PPARα)的转录活性。

材料与方法

在本实验研究中,培养人肝癌(HepG2)细胞,并用不同浓度的tPA和PA(C16:0)进行处理。通过酶法测定细胞内甘油三酯的积累。通过实时聚合酶链反应评估基因表达。在用人胚胎肾293T细胞转染含有PPAR反应元件的载体后,通过荧光素酶报告基因测定法评估PPARα的活性。

结果

当PA和顺式棕榈油酸(cPA)的浓度>1 mM时会降低肝细胞的活力,而tPA则表现出相反的效果,可提高细胞存活率。tPA处理后HepG2细胞中的脂质积累明显低于PA处理的细胞。此外,生理浓度的tPA对SIRT1的表达没有影响,而高浓度时则显著增加其表达。低浓度tPA时PPARα活性有适度增加。

结论

tPA在肝细胞中引起的脂质积累较少,对细胞活力无有害影响,并且可能通过激活SIRT1和诱导PPARα活性而对肝细胞有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/299e/8019128/26af2b52aa75/JRMS-25-105-g001.jpg

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