Diabesity and brain disturbances: A metabolic perspective

The last decades have been marked by an increased prevalence in non-communicable diseases such as obesity and type 2 diabetes (T2D) as well as by population aging and age-related (brain) diseases. The current notion that the brain and the body are interrelated units is gaining the attention of the scientific and medical community. Growing evidence demonstrates that there is a significant overlap in risk, comorbidity, and pathophysiological mechanisms across obesity, T2D and brain disturbances; settings that seem to be worsened when both obesity and T2D occur simultaneously, the so-called diabesity. Thereupon, there is a great concern to critically appraise and understand the mechanisms by which diabesity can affect brain responses, and may accelerate the decline in brain health. In this framework, metabolic disturbances mediated by altered insulin signaling and mitochondrial function arise among the multifactorial interactions described to occur between obesity, T2D and neurocognitive deficits. In this review we have compiled all the notions and evidence describing how diabesity negatively influences brain function putting the emphasis on insulin signaling pathway disturbances and mitochondrial anomalies. We also debate lifestyle interventions as amenable strategies to lessen metabolic anomalies and, consequently, diabesity-associated brain alterations.