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

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.

Keywords:

• n-3 PUFAs
• high-fat diet
• high-fat/fructose diet
• RT-PCR
• obesity
• NLRP3 inflammasome
• mTOR complex

Disclosure statement

The authors declare that they have no conflict of interest.

Funding

This study was performed with the support of the Instituto Politécnico Nacional and the Escuela Superior de Medicina, where molecular biology analyses were performed. NGL was supported by a Ph.D. and CONACYT (246594). ADL, AMG, and ELP are SNI fellows.