The underlying pathological mechanisms of obesity overlap with those of dementia and diabetes mellitus. Age, gender, Western diet, depression, and genetic and epigenetic factors mediate an inflammatory state, which leads to metabolic dysregulation. The development of chronic conditions can be avoided with drugs, surgical interventions, and lifestyle modifications.
Dementia and diabetes mellitus (DM) are chronic diseases closely associated with obesity. This study, published in the International Journal of Molecular Sciences, discussed the factors related to the development of obesity and the role of obesity in the prevalence of dementia and DM. The study addressed an increase in the risk of dementia with a corresponding increase in the onset of DM and obesity. Factors that contribute to the development of obesity include age, gender, genetic factors, epigenetics, and socioeconomic status. Inflammation is evident in obesity and DM, which is further associated with a caloric surplus and the activation of the immune system. The predominant cells that contribute to the inflammatory response are T-cells and macrophages.
NF-kB is an inflammatory mediator that upregulates the expression of pro-inflammatory genes. NK-kB dysregulation in obesity is associated with a chronic inflammatory state and may contribute to developing type 2 DM. The consumption of a high-fat diet leads to the rapid onset of inflammation in the central nervous system (CNS) that offsets the metabolic homeostasis regulated by the hypothalamus, leading to insulin resistance. Insulin resistance in the brain, in the background of diabetes and obesity, also leads to the development of Alzheimer’s disease. Insulin resistance leads to misfolding of tau and aggregation of neurofibrils.
Current research discusses the pharmacological targets of the proopiomelanocortin– melanocortin receptor (POMC–MCR) pathway; protein disulfide isomerase family A, member 4 (Pdia4) molecule; and metformin, a traditional diabetes drug related to the development of diabetes, dementia, and obesity. The drugs targeting the POMC-MCR pathway for treating obesity include MC4R agonists such as Setmelanotide. Metformin is also effective in preventing and treating dementia. Pro-inflammatory Western diets take the lead among the diets that influence obesity and associated pathologies. In contrast, the Mediterranean diet decreases health risks by lowering inflammation. The recommended treatment and prevention strategies for obesity, dementia, and diabetes include lifestyle modifications and pharmacological and surgical interventions.
Selman, A., Burns, S., Reddy, A. P., Culberson, J., & Reddy, P. H. (2022). The Role of Obesity and Diabetes in Dementia. Int J Mol Sci, 23(16). https://doi.org/10.3390/ijms23169267