Evaluation of the interaction between ketone bodies and obesity-associated proteins: an in silico approach

Introduction: Obesity is an upsurge in body fat and is associated with a number of cardiovascular and metabolic conditions, including type-2 diabetes, atherosclerosis, dyslipidaemia, hypertension, and several malignancies. The ketogenic diet, which is high in fat and protein and very low in carbohydrates, has become one of the most researched options for weight loss in recent years. It has also recently gained recognition as a metabolic therapy for its efficacious methods in the prevention and treatment of cancer, type 2 diabetes, obesity, and other illnesses. Methods: This study was carried out to investigate the interaction of ketogenic diet end products, the ketone bodies (acetoacetate, acetone and beta-hydroxybutyrate) and standard drugs (orlistat and cetilistat) on selected obesity-related proteins including ghrelin, leptin, fat mass and obesity-associated (FTO) gene protein (PDB id: 3LFM), catalase, superoxide dismutase and 3-hydroxyl-3-methylgluatarate Co-A (HMG CoA) reductase in vivo. Results: In silico docking simulations of the proteins and ligands (standard drugs and ketone bodies) was done using high computing tools and software. The results revealed varied docking scores based on interactions between the proteins and ligands. The standard drugs and ketone bodies exhibited good docking scores for all the proteins docked, although the standard drugs had slightly higher scores in most cases except for FTO, for which the ketone bodies had higher docking scores. This implies that the FTO–ketone bodies complex might activate the inhibition of fatty acid synthesis, leading to reduction in stored fat. Conclusions: This study concludes that ketone bodies obtained from ketogenic diets may serve as an adjuvant therapy in the management of obesity with a reduced risk of toxicity compared with conventional therapy.