Impaired Brain Insulin Signalling,a Potential Cause of Obesity: A Review of Literature

Abstract

Objective: Obesity is a major health problem in the modern world, which together with other conditions such as cardiovascular disease, hypertension and type 2 diabetes, can pose a direct threat to health and life. Obesity is often accompanied by insulin resistance, which has been shown to occur in both peripheral and central tissues. Brain insulin resistance is a less well understood and less described phenomenon than peripheral insulin resistance, but equally important and worthy of attention. Materials and methods: This review was written using the PubMed database. Articles were searched using keywords such as: insulin resistance, dopamine, obesity, cerebral insulin resistance, mesolimbic pathway, insulin, hypothalamus, feeding. The results of the studies within each phenomenon were analysed, compared and, on this basis, common conclusions were drawn. Results: Available scientific data indicate a correlation between insulin signalling in the brain and the function of the hypothalamic centres of hunger and satiety and the dopaminergic mesolimbic pathway, which is part of the reward system. The phenomenon of hyperphagia in obese individuals with insulin resistance can be explained by potentially reduced hypothalamic satiety signalling with simultaneously increased hunger signalling, and impaired dopaminergic transmission within the mesolimbic pathway, due to impaired insulin activity in the brain. Conclusions: The purpose of this article is to show a new potential direction for future obesity research and treatments, which would be based on the function of insulin-dependent brain centres regulating food intake. Improving insulin signalling in these areas could contribute to reduction in hyperphagia as well as reduction in excessive body weight.