Metabolic syndromes are frequently associated with
dementia, suggesting that the dysregulation of energy metabolism can increase the risk of neurodegeneration and
cognitive impairment. In addition, growing evidence suggests the link between
infections and
brain disorders, including
Alzheimer's disease. The immune system and energy metabolism are in an intricate relationship.
Infection triggers immune responses, which are accompanied by imbalance in cellular and organismal energy metabolism, while metabolic disorders can lead to immune dysregulation and higher
infection susceptibility. In the brain, the activities of brain-resident immune cells, including microglia, are associated with their metabolic signatures, which may be affected by central nervous system (
CNS) infection. Conversely, metabolic dysregulation can compromise innate immunity in the brain, leading to enhanced
CNS infection susceptibility. Thus,
infection and metabolic imbalance can be intertwined to each other in the etiology of
brain disorders, including
dementia.
Insulin and
leptin play pivotal roles in the regulation of immunometabolism in the CNS and periphery, and dysfunction of these signaling pathways are associated with
cognitive impairment. Meanwhile, infectious complications are often comorbid with diabetes and
obesity, which are characterized by
insulin resistance and
leptin signaling deficiency. Examples include human immunodeficiency virus (
HIV) infection and
periodontal disease caused by an oral pathogen Porphyromonas gingivalis. This review explores potential interactions between infectious agents and
insulin and
leptin signaling pathways, and discuss possible mechanisms underlying the relationship between
infection, metabolic dysregulation, and
brain disorders, particularly focusing on the roles of
insulin and
leptin.