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Minerva Endocrinology 2021 September;46(3):309-16

DOI: 10.23736/S2724-6507.21.03460-X


lingua: Inglese

Proinflammatory profile of visceral adipose tissue and oxidative stress in severe obese patients carrying the variant rs4612666 C of NLRP3 gene

Anna PERRI 1 , Danilo LOFARO 1, Antonella LA RUSSA 1, Simona LUPINACCI 1, Giuseppina TOTEDA 1, Achiropita CURTI 2, Antonino URSO 2, Renzo BONOFIGLIO 1, Daniele LA RUSSA 3, Daniela PELLEGRINO 3, Antonio BRUNETTI 4, Emanuela GRECO 4

1 Kidney and Transplantation Research Center, Annunziata Hospital, Cosenza, Italy; 2 Department of General and Bariatric Surgery, Annunziata Hospital, Cosenza, Italy; 3 Department of Biology, Ecology and Earth Sciences (DiBEST), University of Calabria, Rende, Cosenza, Italy; 4 Department Health Sciences, The Magna Græcia University of Catanzaro, Catanzaro, Italy

BACKGROUND: The activation of NLRP3 inflammasome machinery has a central role in obesity-induced inflammation. Genetic studies well support the involvement of functional variants of NLRP3 and its negative regulator, CARD8, in the pathogenesis of complex diseases with an inflammatory background. We have investigated the influence of NLRP3 (rs4612666; rs10754558) and CARD8 (rs204321) genetic variants in both the inflammatory status of visceral adipose tissue (VAT) from patients with severe obesity and in the systemic oxidative stress before and after sleeve-gastrectomy (SLG).
METHODS: Twenty-three consecutive severe obese patients candidate to SLG were enrolled in the study. Visceral adipose tissue (VAT) biopsies, obtained during SLG, were used to evaluate the expression of NLRP3, IL-1β, IL-6, and MCP-1 by real-time RT-PCR. DNA was extracted from peripheral blood lymphocytes and genotyped by RFLP analysis. Before and 3 months after SLG, all patients underwent the assessment of oxidative stress, biochemical parameters, and body composition as measured by bioelectrical impedance analysis (BIA).
RESULTS: Increased expression of NLRP3, IL-6, IL-1β, and MCP-1 mRNA was observed in VAT of rs4612666 C variant carriers, in which higher oxidative stress was also detected as compared to non-carrier individuals. In all patients, oxidative stress, biochemical and BIA parameters improved after SLG, regardless of genotype. No significant correlations were found with the other genetic variants.
CONCLUSIONS: Our results suggest that the NLRP3 rs4612666 C variant may promote a worse pro-inflammatory milieu and higher oxidative stress, thus leading patients to a more severe obesity phenotype. A larger study is needed to confirm this assumption and to investigate the impact of the NLRP3 rs4612666 C variant on severe obesity.

KEY WORDS: Obesity; Polymorphisms, genetic; Oxidative stress; Gastrectomy

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