Obesity and Metabolic Syndrome Affect the Cholinergic Transmission and Cognitive Functions

Background: Worldwide, at least 2.8 million people die each year as a result of being overweight or obese. Obesity leads to metabolic syndrome, a pathological condition characterized by adverse metabolic effects on blood pressure, cholesterol, triglycerides and insulin resistance. Population-based investigations have suggested that obesity and metabolic syndrome may be associated with poorer cognitive performance. Method: A structured search of bibliographic source (PubMed) was undertaken. The following terms "inflammation and obesity and brain", "cholinergic system and obesity", "cholinergic system and metabolic syndrome", "Cognitive impairment and obesity" and "metabolic syndrome and brain" were used as search strings. Results: Over 200 papers, mainly published in the past 10 years were analysed. The major results regarded keyword "metabolic syndrome and brain" followed by, "Cognitive impairment and obesity", "inflammation and obesity and brain", "cholinergic system and obesity" and "cholinergic system and metabolic syndrome". Most papers were pre-clinical but, in general, they were inhomogeneous. Therefore, the results were cited according their contribution to clarify the molecular involvement of obesity and/or metabolic syndrome in cholinergic impairment. Conclusion: This review focuses on the correlation between brain cholinergic system alterations and high-fat diet, describing the involvement of cholinergic system in inflammatory processes related to metabolic syndrome and obesity, which may lead to cognitive decline. Metabolic syndrome has been suggested as a risk factor for cerebrovascular diseases and has been associated with cognitive impairment in different functional brain domains. Preclinical and clinical studies have identified the cholinergic system as a specific target of metabolic syndrome and obesity. The modifications of cholinergic neurotransmission and its involvement in neuro-inflammation may be related to cognitive impairment that affects obese patients.