Neutrophils in obesity: from expansion to dysfunction

Obesity is associated with low-grade chronic inflammation and increased susceptibility to infections. A dysregulated immune response represents a central link between these processes. Neutrophils are key effector cells of the immune system that play essential roles in both inflammatory processes and host defense. Under physiological conditions, neutrophil numbers and functions are tightly regulated to maintain homeostasis. In obesity, however, this regulation becomes disrupted at multiple levels. Obesity promotes a sustained increase in circulating neutrophil numbers through enhanced granulopoiesis and increased release from the bone marrow. Despite this expansion, neutrophils do not exhibit improved antimicrobial capacity. Instead, they display a consistent pattern of functional dysregulation. At baseline, in obesity, neutrophils exhibit increased basal degranulation and extracellular reactive oxygen species production thus contributing to the inflammatory response. Likewise, neutrophil extracellular trap formation is favored in metabolically inflamed tissues, further contributing to inflammation. This apparent enhanced response of neutrophils is coupled with diminished responsiveness to infectious stimuli. While early events such as pathogen recognition and phagocytic uptake seem largely preserved, downstream mechanisms appear impaired. The result is a reduced intracellular microbial killing capacity and diminished neutrophil extracellular trap formation in response to pathogens. This functional dysregulation may be driven at least in part by changes in neutrophil metabolism. Current evidence indicates that metabolic reprogramming during obesity reshapes neutrophil function in a way that promotes inflammation while compromising host defense.