Insulin is a pancreatic hormone secreted to plasma in response to hyperglycemia. Moreover, obesity-related factors are important activators of inflammasome-derived cytokines. These high-molecular-weight factors are responsible for the activation, maturation, and release processes of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Inflammasomes are cytosolic multiprotein complexes that recognize both PAMPs and DAMPs. Adiposity-related inflammatory factors lead to the formation of inflammasome complexes. Innate immune cells such as macrophages can induce inflammatory reactions through detection of pathogen- or danger-associated molecular patterns (PAMPs or DAMPs) using a wide range of pattern-recognition receptors (PRRs). The downregulation of M2 macrophages with anti-inflammatory phenotype and the activation of M1 macrophages with pro-inflammatory phenotype can exaggerate inflammation and insulin resistance in adipocytes. Additionally, adipose tissue also contains numerous immune cells, and its total number increases dramatically with the grade of obesity. Excessive accumulation of fat leads to enhanced expression and release of pro-inflammatory cytokines including tumor necrosis factor α (TNFα), interleukin-6 (IL-6), adipokines, and monocyte chemoattractant protein-1 (MCP-1), which further recruit immune cells to intensify inflammation in adipose tissue. Obesity, characterized by hypertrophy and hyperplasia of adipocytes, is accompanied by chronic local inflammation. Moreover, we also discuss the mechanisms by which the NLRP3 activation potentially links inflammation, peripheral and central insulin resistance, and metabolic changes with AD. The review includes a broadened approach to the role of obesity-related diseases (obesity, low-grade chronic inflammation, type 2 diabetes, insulin resistance, and enhanced NLRP3 activity) in AD. NLRP3/IL-1β signaling could underlie the association between adiposity and cognitive impairment in humans. The abnormal activation of the NLRP3 signaling pathway influences neuroinflammatory processes. Activation of the inflammasome complex, particularly NLRP3, has a crucial role in obesity-induced inflammation, insulin resistance, and T2DM. Adiposity-related inflammatory factors lead to the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of the pro-inflammatory cytokines including interleukin-1β (IL-1β) and interleukin-18 (IL-18). Adiposity is associated with the pro-inflammatory phenotype.
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AD, obesity, and T2DM share similar features such as chronic inflammation, increased oxidative stress, insulin resistance, and impaired energy metabolism. Metabolic disorders including obesity and type 2 diabetes mellitus (T2DM) may stimulate amyloid β (Aβ) aggregate formation. Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia.