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Background: Obesity and being overweight have been described as potential causes of neurological disorders. Leptin, a peptide expressed in fat tissue, importantly participates in energy homeostasis and storage and has recently been identified for its signaling receptors in neuronal circuits of the brain. Aim: To elucidate whether the endogenous modulation of leptin can be a protection against neuropsychiatric disorders. Method: A systematic review was performed in accordance with the PRISMA-P method, and reports of studies containing data of leptin concentrations in healthy individuals with or without obesity were retrieved from the PubMed database, using the combinations of Mesh terms for “Leptin” and “Metabolism”. Results: Forty-seven randomized and non-randomized controlled trials, dating from 2000 to 2021, were included in the qualitative synthesis. Discussion and conclusions: Leptin secretion displays a stabilizing pattern that is more sensitive to a negative energy intake imbalance. Leptin levels influence body weight and fat mass as a pro-homeostasis factor. However, long-term exposure to elevated leptin levels may lead to mental/behavioral disorders related to the feeding and reward systems.

Leptin—A Potential Bridge between Fat Metabolism and the Brain’s Vulnerability to Neuropsychiatric Disorders: A Systematic Review