Gamma-oryzanol as a possible PPAR-γ agonist in adipose tissue may represents a coadjutant therapeutic to prevent cytokine storm in COVID-19 obese patients

Francisqueti-Ferron, Fabiane Valentini; Garcia, Jéssica Leite; Togneri Ferron, Artur Junio; Nakandakare- Maia, Erika Tiemi; Gregolin, Cristina Schmitt; Paixão das Chagas Silva, Janaina; Carolo dos Santos, Klinsmann; Colombo Lo, Ângelo Thompson; Siqueira, Juliana Silva; de Mattei, Letícia; Henrique de Paula, Bruno; Sarzi, Felipe; Vágula de Almeida Silva, Carol Cristina; Moreto, Fernando; Costa, Mariane Róvero; Lucia A Ferreira, Ana; Minatel, Igor Otávio; Correa, Camila Renata

The literature has reported a higher prevalence of negative clinical outcomes due to Coronavirus disease 19 (COVID-19) in obese individuals. This can be explained by the cytokine storm, result from the cytokine production from both obesity and viral infection. Gamma-oryzanol (γOz) is a compound with anti-inflammatory and antioxidant activities. However, little is known about the γOz action as a possible agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). The aim of this study was to test the hypothesis that γOz attenuates the cytokine storm by stimulating PPAR-γ in the adipose tissue. METHODS: Male Wistar rats were randomly divided into three experimental groups and fed ad libitum for 30 weeks with control diet (C, n = 6), high sugar- fat diet (HSF, n = 6) or high sugar- fat diet + γOz (HSF + γOz, n = 6). HSF groups also received water + sucrose (25%). The γOz dose was 0.5% in the chow. Evaluation in animals included caloric intake, body weight, adiposity index, plasma triglycerides, and HOMA-IR. In adipose tissue was evaluated: PPAR-γ gene and protein expression, inflammatory and oxidative stress parameters, and histological analysis. RESULTS: Adipose tissue dysfunction was observed in HSF group, which presented remarkable PPAR-γ underexpression and increased levels of cytokines, other inflammatory markers and oxidative stress. The γOz treatment prevented adipose tissue dysfunction and promoted PPAR-γ overexpression. CONCLUSION: Natural compounds as γOz can be considered a coadjutant therapy to prevent the cytokine storm in COVID-19 patients with obesity conditions.