Ketogenesis and SIRT1 as a tool in managing obesity

Obesity is a serious chronic disease and a public health concern in both developing and developed countries. Managing obesity has been a great challenge for both health care professionals and patients alike. Among the various diet programs aimed at promoting weight loss, the ketogenic diet, a diet high in fat and low in carbohydrates, has been at the forefront recently and its mechanism in weight loss is much debated. Activation of Sirtuin 1 or SIRT1 is able to circumvent various diseases, including metabolic syndrome and obesity and is thought to be a potentially reliable treatment target for both of them. Augmentation of SIRT1 may be carried out using dietary means such as nicotinamide adenine dinucleotide (NAD) supplementation and/or ketogenic diet. Although ketogenic diet may augment SIRT1 activation in people affected by obesity, recent studies have indicated that the relationship between SIRT1 and ketogenesis is unpredictable. The exact circumstances and mechanisms of SIRT1, NAD and ketogenesis in the clinical setting as an intervention tool in managing obesity remained uncertain. Although several recent literatures have documented significant weight-loss following ketogenic diet interventions, there were limitations with regards to duration of trial, choice and the number of trial subjects. Studies investigating the safety of ketogenic diet in the long term, beyond 46 weeks and related mechanism and pathways are still lacking and the sustainability of this diet remains to be determined. This review explores the recent progress on ketogenic diet and its relationships with SIRT1 as a tool in managing obesity and relevant clinical implications.