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Chronic inflammation in obesity is a link between obesity and secondary disease. While macrophages and monocytes are known to contribute to metabolic disease risk during diet exposure, little is known about the contribution of neutrophils. We assessed the impact of obesity on neutrophils using a 16-week model of diet-induced obesity. Bone marrow (BM) neutrophils significantly expanded with chronic high-fat diet (HFD), significantly decreased TNF\u0251 protein release, and impaired neutrophil regenerative function compared to normal diet (ND) neutrophils. scRNAseq and flow cytometry demonstrated HFD neutrophil heterogeneity and validated that these cells do not have elevated expression of proinflammatory genes without secondary stimulation. HFD neutrophils showed elevated expression of genes associated with lipid metabolism\u2014acyl-CoA thioesterase 1 (Acot1), carnitine palmitoyltransferase 1a (Cpt1a), and perilipin 2 (Plin2). Consistent with the importance of lipid metabolism in driving dysfunction, neutrophils from HFD-fed animals and neutrophils treated with palmitate had impaired bacterial phagocytosis and killing responses. These data shed light on the complex regulation of intracellular lipids and the role of metabolism on neutrophil function during homeostasis and disease.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf024","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T12:09:36Z","timestamp":1742213376000},"page":"680-693","source":"Crossref","is-referenced-by-count":13,"title":["High fat diet feeding impairs neutrophil phagocytosis, bacterial killing, and neutrophil-induced hematopoietic regeneration"],"prefix":"10.1093","volume":"214","author":[{"given":"Emily","family":"Bowers","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Michigan Medical School , Ann Arbor, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle P","family":"Entrup","sequence":"additional","affiliation":[{"name":"Immunology Graduate Program, University of Michigan Medical School , Ann Arbor, MI,","place":["United 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