Investigation of calonysterone and 20-hydroxyecdysone effects in high-fat, high-sugar diet-induced obesity rat model

Osman, Alaa A. M. and Laczkó, Dávid and Vágvölgyi, Máté and Seres-Bokor, Adrienn and Sztojkov-Ivanov, Anita and Kemény, Kata Kira and Hunyadi, Attila and Ducza, Eszter (2025) Investigation of calonysterone and 20-hydroxyecdysone effects in high-fat, high-sugar diet-induced obesity rat model. HELIYON, 11 (3). ISSN 2405-8440

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Abstract

Globally, the incidence of obesity among adults has significantly risen since 1990, with a more than twofold rise in prevalence. Similarly, the incidence of obesity among adolescents has increased fourfold. Overweight constitutes a significant health and social issue in developed nations globally. Conventional therapies such as lifestyle modification (nutrition and physical activity) have limited weight reduction. Drug therapy is often not possible or cannot be afforded due to poor patient compliance or therapeutic side effects. 20-hydroxyecdysone (20E) is a worldwide used ‘green anabolic’ dietary supplement that has beneficial effects in some animal models of metabolic diseases. Our ongoing research examines the impacts of 20E and calonysterone (CAL) in an animal model with a diet high in fats and sugars (HFHSD). Glucose tolerance tests assessed prediabetic status and RT-PCR and Western blot analysis determined interleukin-6 (IL6) expression. The concertations of superoxide dismutase, catalase, adiponectin, leptin, and IL-6 were quantified by ELISA. Total antioxidant capacity was assessed using a colorimetric assay kit, and global DNA methylation was also measured. CAL entirely prevented HFHSD-induced obesity and decreased the inflammatory cytokine (IL6) level and antioxidant activity in our model. Both 20E and CAL normalized the changed plasma concentration of adiponectin and leptin after the HFHS diet. The administration of CAL and 20E in obese rats significantly increased the percent of total DNA methylation. This is the first in vivo study on this natural ecdysteroid, which may offer new alternatives for treating metabolic diseases. Based on our findings, we are supposed to show new preventive possibilities for overweight-induced chronic progressive diseases.

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