{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:39:30Z","timestamp":1791095970467,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Extensive evidence indicates that nutrient excess associated with obesity and type 2 diabetes activates innate immune responses that lead to chronic, sterile low-grade inflammation, and obese and diabetic humans also have deficits in wound healing and increased susceptibility to infections. Nevertheless, the mechanisms that sustain unresolved inflammation during obesity remain unclear. In this study, we report that saturated free fatty acids that are elevated in obesity alter resolution of acute sterile inflammation by promoting neutrophil survival and decreasing macrophage phagocytosis. Using a targeted mass spectrometry\u2013based lipidomics approach, we found that in db\/db mice, PGE2\/D2 levels were elevated in inflammatory exudates during the development of acute peritonitis. Moreover, in isolated macrophages, palmitic acid stimulated cyclooxygenase-2 induction and prostanoid production. Defects in macrophage phagocytosis induced by palmitic acid were mimicked by PGE2 and PGD2 and were reversed by cyclooxygenase inhibition or prostanoid receptor antagonism. Macrophages isolated from obese-diabetic mice expressed prostanoid receptors, EP2 and DP1, and contained significantly higher levels of downstream effector, cAMP, compared with wild-type mice. Therapeutic administration of EP2\/DP1 dual receptor antagonist, AH6809, decreased neutrophil accumulation in the peritoneum of db\/db mice, as well as the accumulation of apoptotic cells in the thymus. Taken together, these studies provide new insights into the mechanisms underlying altered innate immune responses in obesity and suggest that targeting specific prostanoid receptors may represent a novel strategy for resolving inflammation and restoring phagocyte defects in obese and diabetic individuals.<\/jats:p>","DOI":"10.4049\/jimmunol.1203369","type":"journal-article","created":{"date-parts":[[2013,6,20]],"date-time":"2013-06-20T04:36:02Z","timestamp":1371702962000},"page":"1383-1392","source":"Crossref","is-referenced-by-count":84,"title":["Increased Saturated Fatty Acids in Obesity Alter Resolution of Inflammation in Part by Stimulating Prostaglandin Production"],"prefix":"10.1093","volume":"191","author":[{"given":"Jason","family":"Hellmann","sequence":"first","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville School of Medicine , Louisville, KY 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Zhang","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville School of Medicine , Louisville, KY 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunan","family":"Tang","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville School of Medicine , Louisville, KY 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhavi","family":"Rane","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Louisville School of Medicine , Louisville, KY 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruni","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville School of Medicine , Louisville, KY 40202"},{"name":"Division of Cardiovascular Medicine, Department of Medicine, Institute of Molecular Cardiology, University of Louisville School of Medicine , Louisville, KY 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Spite","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville School of Medicine , Louisville, KY 40202"},{"name":"Division of Cardiovascular Medicine, Department of Medicine, Institute of Molecular Cardiology, University of Louisville School of Medicine , Louisville, KY 40202"},{"name":"Department of Microbiology and Immunology, University of Louisville School of Medicine , Louisville, KY 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,1]]},"reference":[{"key":"2025032405132761100_r1","first-page":"1066","article-title":"Prevalence of overweight and obesity among adults with diagnosed diabetes: United States, 1988\u20131994 and 1999\u20132002","volume":"53","author":"Centers for Disease Control and Prevention (CDC)","year":"2004","journal-title":"MMWR Morb. 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