Connecting the dots between sleep deprivation and obesity: the role of melatonin in appetite regulation and insulin sensitivity from a mechanistic review perspective.

This review aims to clarify the mechanistic links between sleep deprivation, appetite regulation, and insulin sensitivity, and to explore the role of melatonin in these pathways. A systematic search identified 82 relevant studies, which were critically and thematically analysed. Evidence indicates that sleep deprivation lowers melatonin levels, which impairs insulin sensitivity via disruptions in the IRS/PI3K/AKT and cAMP/PKA/CREB pathways. Melatonin interventions appear to influence these pathways and affect leptin and appetite-regulating neuropeptides such as POMC, AgRP, and NPY, although findings on the direction of these effects remain mixed. Intervention studies using melatonin doses of ≤5 mg/day for at least four weeks show potential for reducing body weight in humans. Overall, this review highlights the complex interactions between sleep deprivation, appetite regulation, insulin sensitivity, and obesity, and suggests that melatonin may offer a promising adjunctive approach, although further research is needed to resolve conflicting results and support evidence based practice.