{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:05:51Z","timestamp":1790247951032,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Dynamic regulation of protein synthesis is essential for metabolic homeostasis, with translation initiation playing a key role in this process. Emerging evidence strongly indicates that in addition to canonical eukaryotic initiation factors (e.g., eIF2, eIF4E) non\u2010canonical factors, such as eukaryotic initiation factor 2A can modulate metabolic homeostasis. eIF2A is a highly conserved eukaryotic protein originally proposed to function analogously to bacterial IF2, promoting initiator Met\u2010tRNAi recruitment to the 40S ribosomal subunit, though its precise mechanism remains debated. To investigate its organismal role, we have previously generated the total\u2010body eIF2A knockout mouse, which revealed eIF2A functions in lipid homeostasis, glucose tolerance, insulin sensitivity, and susceptibility to metabolic syndrome. To further determine whether adipose tissue drives these phenotypes, we presently generated adipose\u2010specific eIF2A knockout mice. Despite dysregulation of some key adipokines, including for example, adiponectin, these mice did not develop metabolic syndrome, even under high\u2010fat diet conditions, indicating that adipose tissue specific deficiency of eIF2A is insufficient to reproduce the metabolic defects observed in total\u2010body knockout. However, we found that eIF2A deficiency in the liver of the total body eIF2A\u2010KO mice can independently drive metabolic syndrome components via translational control of Lpin1 (a phosphatidate phosphatase and a transcriptional coactivator) that controls hepatic lipid storage and metabolism. eIF2A deficiency in the liver leads to disruption of fatty acid oxidation and the production of ketone bodies, not observed in adipose\u2010specific eIF2A knockout mice. Our findings suggest that systemic metabolic effects observed in the total body eIF2A\u2010KO mice may arise from coordinated functions across multiple organs.<\/jats:p>","DOI":"10.1096\/fba.2026-00271","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:33:17Z","timestamp":1788849197000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Conditional\n                    <scp>eIF2A<\/scp>\n                    Deletion Suggests Extra\u2010Adipose Mechanisms Underlying Metabolic Syndrome in Total\u2010Body\n                    <scp>eIF2A<\/scp>\n                    Knockout Mice"],"prefix":"10.1096","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3116-9418","authenticated-orcid":false,"given":"Adedeji Isaac","family":"Adeloye","sequence":"first","affiliation":[{"name":"Center for Gene Regulation in Health and Disease, Department of Biological, Geological and 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