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It has been shown that\n                      <jats:italic toggle=\"yes\">Trypanosoma cruzi<\/jats:italic>\n                      targets adipose tissues and resides in adipocytes. However, how\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      manipulates adipocytes to redirect nutrients for its benefit remains unknown. Here, we uncover the role of FABP4 in facilitating\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      infection in murine 3T3-L1 adipocytes. We demonstrate that pharmacological or genetic inhibition of FABP4, carnitine palmitoyltransferase I (CPT-1), or fatty acid oxidation (FAO) abrogates the intracellular growth of\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      in adipocytes. We also found that inhibiting FABP4, CPT-1, or FAO eliminates the infection-induced elevation of mitochondrial and cellular reactive oxygen species (ROS) in adipocytes. Furthermore,\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      infection-induced elevation of ROS in adipocytes increased the cytosolic Fe\n                      <jats:sup>2+<\/jats:sup>\n                      , which fueled\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      proliferation. The treatment with antioxidants such as ROS scavenger N-acetyl cysteine (NAC) or mitochondrial ROS inhibitors MitoQ increased the expression level of mRNA for Ferroportin and Ferritin, leading to the decrease in cytosolic Fe\n                      <jats:sup>2+<\/jats:sup>\n                      and the intracellular growth inhibition of\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      in adipocytes. The addition of ferrous sulfate reversed the FABP4 inhibitor or antioxidant-induced decrease in adipocyte parasite burden. Our results demonstrate that\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      exploits host FABP4 to facilitate fatty acid oxidation and elevate cellular ROS, increasing the labile iron pool for the intracellular replication of\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      in adipocytes. These results highlight the therapeutic possibility of host FABP4 as a drug target for\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Persistent infection with a protozoan parasite\n                        <jats:italic toggle=\"yes\">, Trypanosoma cruzi,<\/jats:italic>\n                        causes Chagas disease. While it has been appreciated that adipose tissues are one of the sites of persistent infection, the mechanism of how the parasite survives in adipocytes remains to be established. Our study highlights FABP4, a key regulator of metabolic dysfunction and inflammation, as a therapeutic host target controlling\n                        <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                        infection in adipocytes. We uncover the importance of FABP4 for\n                        <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                        replication in mouse adipocytes through engagement with lipid droplet degradation and trafficking of liberated free fatty acids to the host cell\u2019s mitochondria, which are utilized for fatty acid oxidation (FAO).\n                        <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                        infection-induced FAO fuels reactive oxygen species, and the subsequent iron mobilization accelerates parasite replication. These results shed light on the mechanisms of\n                        <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                        persistent infection in adipocytes, raising the possibility of host FABP4 as a drug target for\n                        <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                        infection.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02180-25","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T12:00:29Z","timestamp":1757332829000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["FABP4-dependent fatty acid oxidation-fueled mitochondrial ROS induces the mobilization of cellular iron and facilitates\n                    <i>Trypanosoma cruzi<\/i>\n                    proliferation in murine adipocytes"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8696-4959","authenticated-orcid":false,"given":"Kazunari","family":"Ishii","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04nt8b154","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology & Immunology, Faculty of Medicine, Fukuoka University","place":["Fukuoka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kurihara","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04nt8b154","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology & Immunology, Faculty of Medicine, Fukuoka University","place":["Fukuoka, 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