Abstract
Increased life expectancy in combination with modern life style and high prevalence of obesity are important risk factors for development of neurodegenerative diseases. Neuroinflammation is a feature of neurodegenerative diseases, and microglia, the innate immune cells of the brain, are central players in it. The present review discusses the effects of obesity, chronic peripheral inflammation and obesity-associated metabolic and endocrine perturbations, including insulin resistance, dyslipidemia and increased glucocorticoid levels, on microglial function.
Highlights
The effects of obesity are not limited to the periphery and strongly affect neuronal and innate immune functions in the brain
Circulating immune cells, proinflammatory cytokines, adipokines, dyslipidemia, glucocorticoids and bacterial endotoxins are some of the factors generating a systemic environment unfavorable for microglial homeostatic function
The link between metabolic disease and neurodegeneration is well supported by clinical data, less is known on the underlying mechanisms
Summary
Obesity is a major health problem reaching worldwide pandemic proportions [1,2] It is a result of the modern lifestyle, which is characterized by reduced physical activity and increased energy intake [1,2]. It constitutes an important health challenge as it substantially increases the risk for development of life-threatening conditions, such as type 2 diabetes mellitus, fatty liver disease, atherosclerosis, myocardial infarction and stroke [1,2]. The present review analyzes how obesity may promote microglia-mediated neuroinflammation and associated neurodegeneration through immune, metabolic and endocrine mechanisms.
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