n-3脂肪酸可调节高脂或高脂/果糖饮食喂养大鼠肝脏中Nlrp3炎性小体和mTOR的mRNA表达。

n-3 Fatty acids modulate the mRNA expression of the Nlrp3 inflammasome and Mtor in the liver of rats fed with high-fat or high-fat/fructose diets.

作者信息

Garay-Lugo Natalia, Domínguez-Lopez Aarón, Miliar García Angel, Aguilar Barrera Eliud, Gómez López Modesto, Gómez Alcalá Alejandro, Martínez Godinez Maria de Los Angeles, Lara-Padilla Eleazar

机构信息

a Laboratorio de Biología Molecular , Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis and Salvador Díaz Mirón , México , D.F , México ;

b Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis and Díaz Mirón , México , D.F , México.

出版信息

Immunopharmacol Immunotoxicol. 2016 Oct;38(5):353-63. doi: 10.1080/08923973.2016.1208221.

DOI:10.1080/08923973.2016.1208221

PMID:27367537

Abstract

CONTEXT

There is evidence that n-3 polyunsaturated fatty acids (n-3-PUFAs) can inhibit mTORC1, which should potentiate autophagy and eliminate NLRP3 inflammasome activity.

OBJECTIVE

Evaluate the effect of a high-fat or high-fat/fructose diet with and without n-3-PUFAs on hepatic gene expression.

MATERIALS AND METHODS

We examined the mRNA expression by RT-PCR of Mtor, Nlrp3, and other 22 genes associated with inflammation in rats livers after a 9-week diet. The dietary regimens were low-fat (control, CD), high-fat (HF), high-fat/fructose (HF-Fr), and also each of these supplemented with n-3-PUFAs (CD-n-3-PUFAs, HF-n-3-PUFAs, and HF-Fr-n-3-PUFAs). These data were processed by GeneMania and STRING databases.

RESULTS

Compared to the control, the HF group showed a significant increase (between p < 0.05 and p < 0.0001) in 20 of these genes (Il1b, Il18, Rxra, Nlrp3, Casp1, Il33, Tnf, Acaca, Mtor, Eif2s1, Eif2ak4, Nfkb1, Srebf1, Hif1a, Ppara, Ppard, Pparg, Mlxipl, Fasn y Scd1), and a decrease in Sirt1 (p < 0.05). With the HF-Fr diet, a significant increase (between p < 0.05 and p < 0.005) was also found in the expression of 16 evaluated genes (Srebf1, Mlxipl, Rxra, Abca1, Il33, Nfkb1, Hif1a, Pparg, Casp1, Il1b, Il-18, Tnf, Ppard, Acaca, Fasn, Scd1), along with a decrease in the transcription of Mtor and Elovl6 (p < 0.05). Contrarily, many of the genes whose expression increased with the HF and HF-Fr diets did not significantly increase with the HF-n-3-PUFAs or HF-Fr-n-3-PUFAs diet.

DISCUSSION AND CONCLUSION

We found the interrelation of the genes for the mTORC1 complex, the NLRP3 inflammasome, and other metabolically important proteins, and that these genes respond to n-3-PUFAs.

摘要

背景

有证据表明，n-3多不饱和脂肪酸（n-3-PUFAs）可抑制mTORC1，这应能增强自噬并消除NLRP3炎性小体活性。

目的

评估高脂或高脂/果糖饮食（含或不含n-3-PUFAs）对肝脏基因表达的影响。

材料与方法

在大鼠经过9周饮食后，我们通过逆转录聚合酶链反应（RT-PCR）检测了肝脏中Mtor、Nlrp3以及其他22个与炎症相关基因的mRNA表达。饮食方案包括低脂饮食（对照组，CD）、高脂饮食（HF）、高脂/果糖饮食（HF-Fr），并且这些饮食方案均添加n-3-PUFAs（CD-n-3-PUFAs、HF-n-3-PUFAs和HF-Fr-n-3-PUFAs）。这些数据通过GeneMania和STRING数据库进行处理。

结果

与对照组相比，HF组中20个基因（Il1b、Il18、Rxra、Nlrp3、Casp1、Il33、Tnf、Acaca、Mtor、Eif2s1、Eif2ak4、Nfkb1、Srebf1、Hif1a、Ppara、Ppard、Pparg、Mlxipl、Fasn和Scd1）有显著增加（p值在<0.05至<0.0001之间），而Sirt1减少（p<0.05）。对于HF-Fr饮食，在16个评估基因（Srebf1、Mlxipl、Rxra、Abca1、Il33、Nfkb1、Hif1a、Pparg、Casp1、Il1b、Il-18、Tnf、Ppard、Acaca、Fasn、Scd1）的表达中也发现有显著增加（p值在<0.05至<0.005之间），同时Mtor和Elovl6的转录减少（p<0.05）。相反，许多在HF和HF-Fr饮食中表达增加的基因，在HF-n-3-PUFAs或HF-Fr-n-3-PUFAs饮食中并未显著增加。