Chronic Low-Grade Inflammation in Obesity and Type 2 Diabetes and the Roles of Adipokines, NLRP3 and Immunometabolism

Chronic low-grade inflammation links nutrient excess to altered insulin action, but its mechanisms depend on tissue, cell type and metabolic context. Evidence was assessed across adipose immune cells, adipokines, NLRP3 inflammasome activation and cellular metabolic programs in obesity and type 2 diabetes. Experimental studies demonstrate that macrophage function and inflammasome signaling can alter metabolic phenotypes, while human tissue studies support associations between inflammation and insulin resistance. Lipid species, mitochondrial signals and metabolites such as lactate and succinate provide connections between nutrient handling and immune responses. These connections are not uniformly harmful: the same signaling system can produce different effects in distinct tissues or physiological states. Trials of interleukin-1β inhibition show that lowering inflammation does not necessarily prevent diabetes, emphasizing the distinction between a mechanistic target and a validated clinical indication. Successful translation requires cell-specific causal experiments, human target-engagement studies and outcomes that extend beyond inflammatory biomarkers.