Molecular mechanisms underlying obesity-altered brain functions: the alteration of BDNF production

Abstract

Obesity adversely impacts the quality of life; people with obesity are more vulnerable to chronic diseases such as T2DM, insulin resistance, and dementia. Brain-derived neurotrophic factor (BDNF) has a significant role in cognition and brain health; it influences synaptic plasticity and neurogenesis. BDNF has been proposed as mechanistic a modulator to explain the association between peripheral dysmetabolism and cognitive decline. This review highlights the metabolic alterations associated with obesity including, insulin resistance, inflammation, and BDNF levels. It illustrates, as well, the mechanistic crosstalk between adiposity and the decline of brain health and cognition explained by the BDNF alteration. A narrative review of the recent research focusing on BDNF molecular biology and functions, the effect of obesity on its regulation, and neuronal health and cognition during obesity and its allied metabolic changes. Although the results of the related published research were contradicted, obesity was related to BDNF expression and signaling dysregulation. This dysregulation leads to neuroinflammation a condition that impairs synaptic plasticity and neurogenesis, and increases apoptosis. These fluctuations were linked to cognitive decline and different types of neurodegeneration. Insulin resistance and hyperinsulinemia were the main hubs for connecting adiposity, BDNF, and dementia. Correction of BDNF expression and signaling may offer an evolving therapeutic practice for the treatment and prevention of obesity-related cognitive decline. Further longitudinal and clinical trial studies are needed to clarify the causal direction and expand our vision of treatment and prevention regimes for cognitive disorders.