{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:06:34Z","timestamp":1788311194498,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004423","name":"Waseda University","doi-asserted-by":"publisher","award":["2013B\u2010174"],"award-info":[{"award-number":["2013B\u2010174"]}],"id":[{"id":"10.13039\/501100004423","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004423","name":"Waseda University","doi-asserted-by":"publisher","award":["2014B\u2010313"],"award-info":[{"award-number":["2014B\u2010313"]}],"id":[{"id":"10.13039\/501100004423","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004423","name":"Waseda University","doi-asserted-by":"publisher","award":["2015B\u2010323"],"award-info":[{"award-number":["2015B\u2010323"]}],"id":[{"id":"10.13039\/501100004423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Limited oxygen availability impairs normal body growth, although the underlying mechanisms are not fully understood. In <jats:italic>Drosophila<\/jats:italic>, hypoxic responses in the larval fat body (FB) disturb the secretion of insulin\u2010like peptides from the brain, inhibiting body growth. However, the cell\u2010autonomous effects of hypoxia on the insulin\u2010signaling pathway in larval FB have been underexplored. In this study, we aimed to examine the effects of overexpression of <jats:italic>Sima<\/jats:italic>, a <jats:italic>Drosophila hypoxia<\/jats:italic>\u2010<jats:italic>inducible factor<\/jats:italic>\u2010<jats:italic>1 (HIF<\/jats:italic>\u2010<jats:italic>1) \u03b1<\/jats:italic> homolog and a key component of HIF\u20101 transcription factor essential for hypoxic adaptation, on the insulin\u2010signaling pathway in larval FB. Forced expression of <jats:italic>Sima<\/jats:italic> in FB reduced the larval body growth with reduced Akt phosphorylation levels in FB cells and increased hemolymph sugar levels. <jats:italic>Sima<\/jats:italic>\u2010mediated growth inhibition was reversed by overexpression of <jats:italic>TOR<\/jats:italic> or suppression of <jats:italic>FOXO<\/jats:italic>. After <jats:italic>Sima<\/jats:italic> overexpression, larvae showed higher expression levels of <jats:italic>Tribbles<\/jats:italic>, a negative regulator of Akt activity, and a simultaneous knockdown of <jats:italic>Tribbles<\/jats:italic> completely abolished the effects of <jats:italic>Sima<\/jats:italic> on larval body growth. Furthermore, a reporter analysis revealed <jats:italic>Tribbles<\/jats:italic> as a direct target gene of <jats:italic>Sima<\/jats:italic>. These results suggest that <jats:italic>Sima<\/jats:italic> in FB evokes <jats:italic>Tribbles<\/jats:italic>\u2010mediated insulin resistance and consequently protects against aberrant insulin\u2010dependent larval body growth under hypoxia.<\/jats:p>","DOI":"10.1111\/gtc.12913","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T06:25:23Z","timestamp":1639722323000},"page":"145-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<i>Sima<\/i>, a <i>Drosophila<\/i> homolog of <i>HIF\u20101\u03b1<\/i>, in fat body tissue inhibits larval body growth by inducing <i>Tribbles<\/i> gene expression"],"prefix":"10.1111","volume":"27","author":[{"given":"Koji","family":"Noguchi","sequence":"first","affiliation":[{"name":"Department of Life Sciences and Medical BioScience Waseda University School of Advanced Science and Engineering Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyosuke","family":"Yokozeki","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Medical BioScience Waseda University School of Advanced Science and Engineering Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Medical BioScience Waseda University School of Advanced Science and Engineering Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Medical BioScience Waseda University School of Advanced Science and Engineering Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Medical BioScience Waseda University School of Advanced Science and Engineering Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Regulation and Genetics Institute for Molecular and Cellular Regulation Gunma University Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0295-4257","authenticated-orcid":false,"given":"Nobuhito","family":"Goda","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Medical BioScience Waseda University School of Advanced Science and Engineering Tokyo 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