Involvement of Fat Mass and Obesity Gene (FTO) in the Anti-Obesity Action of Annona muricata Annonaceae: In Silico and in Vivo Studies

Background: Annona muricata (Annonaceae) known as soursop is a common tropical plant species known for its numerous medicinal properties including obesity. The underlying mechanism of anti-obesity effect of A. muricata was investigated. The fat mass and obesity associated protein (FTO) is a validated potential target for anti-obesity drugs.

Methods: The interaction of compounds previously characterized from A. muricata was investigated against FTO using Autodock Vina. Also, modulation of FTO and STAT-3 mRNA expression by A. muricata was investigated in high fat diet induced obese rats (HFDR) using RT-PCR.

Results: A significant up-regulation of FTO gene was observed in HFDR when compared to control rats, while administration of A. muricata (200 mg/kg) significantly (p < 0.05) down-regulated FTO gene expression when compared to HFDR group. The effect of obesity on STAT-3 gene expression was also reversed by A. muricata (200 mg/kg). In silico study revealed annonaine and annonioside (-9.2 kcal/mol) exhibited the highest binding affinity with FTO, followed by anonaine and isolaureline (-8.6 kcal/mol). Arg-96 is a critical amino acid enhancing anonaine, isolaureline-FTO binding.

Conclusion: This study suggests the possible anti-obesity mechanism of A. muricata is via down-regulation of FTO with concomitant up-regulation of STAT-3 genes. This study confirmed the use of this plant in the management of obesity and the probable compounds responsible for its antiobesity effect are annonaine and annonioside.

Keywords: Annona muricata; FTO and STAT-3 genes; Molecular docking; Obesity.