Introduction

The NLRP3 inflammasome plays a significant role in the pathogenesis of obesity by contributing to the development of chronic low-grade inflammation, systemic inflammation, and, consequently, neuroinflammation.

Quercetin is a flavonoid which possesses anti-inflammatory properties, therefore representing a potential modulator of neuroinflammatory process, metabolic regulators such as the fat mass obesity-associated gene (Fto) and TNF-α/NF-κB/NLRP3 Inflammasome pathway genes.

Studies in animal models have shown that quercetin exerts a wide range of effects over inflammatory processes, suggesting potential therapeutical applications. Fto is a well-known gene associated with obesity risk, body mass index, energy homeostasis and hypothalamic control of appetite and satiety. Altered Fto expression influences metabolic and inflammatory responses and plays a relevant role in inflammatory-related diseases.

We hypothesized that quercetin inhibits overexpression of Fto and the activation of the TNF-α/NF-κB/NLRP3 Inflammasome pathway in the hypothalamus of high-fat-diet Wistar rats.

Objectives

To evaluate mRNA expression of Fto and components of the TNF-α/NF-κB/NLRP3 inflammasome pathway in the hypothalamus of high-fat diet-fed Wistar rats by quantitative PCR (qPCR).

Methodology

After 2 weeks of acclimation, three groups of Wistar rats (200 ± 20 g) were randomly assigned to three groups (n = 6 each group): (a) standard diet (SD), (b) high-fat diet (HD), and (c) high-fat diet with quercetin (HD+Q). Quercetin was administered intragastrically at a dose of 50 mg/kg/day for 12 weeks.

At the end of the intervention period, rats were euthanized and the hypothalamus was collected. Total RNA was isolated using the TriZol method, purified with isopropanol and 75% ethanol, quantified, and its purity verified by nanodrop 2000 spectrophotometer.

cDNA was synthetized from 100 ng of total RNA using random primers. The mRNA expressions of Fto, Tnf, Tnfrs1a, Tradd, Ripk1, Map3k7, Ikbkb, Ikbkg, Nek7, Nfkbia, Nlrp3, Pycard, Casp1, Il1b and Il18 through qPCR. Β-Actin were used as housekeeping genes.

Results

The HD+Q group showed a significant decrease in the mRNA expression of Fto and pro-inflammatory genes involved in the TNF-α/NF-κB/NLRP3 inflammasome pathway compared with the HD group. In contrast, the HD group showed a significant increase in the expression of these genes relative to the SD group.

Conclusions

Quercetin downregulates mRNA expression of Fto and key components of the TNF-α/NF-κB/NLRP3 inflammasome pathway in the hypothalamus of high-fat-diet-fed Wistar rats. These findings suggest that quercetin may represent a promising therapeutic candidate for targeting obesity-associated neuroinflammation.