{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T21:31:13Z","timestamp":1784842273695,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Insulin-like growth factor 1 (IGF1) is an essential effector of the growth hormone (GH)\/IGF1 axis for somatic growth regulation in mammals. However, its functions have not been thoroughly investigated in zebrafish <jats:italic>in vivo<\/jats:italic>. In this study, the <jats:italic>igf1<\/jats:italic>-deficient zebrafish model was developed using the CRISPR\/Cas9 technique. In this study all the results were performed on both male and female animals. The growth of both male and female <jats:italic>igf1<\/jats:italic>-deficient zebrafish were reduced. The <jats:italic>igf1<\/jats:italic> deficiency leads to significant complementary up-regulation of transcriptional expression levels of <jats:italic>insulin, igf2<\/jats:italic> and <jats:italic>igf3<\/jats:italic>. This suggested that <jats:italic>igf2<\/jats:italic> and <jats:italic>igf3<\/jats:italic> may act with redundant functions. While the upregulation of <jats:italic>gh1<\/jats:italic> expression can only be detected in <jats:italic>igf1<\/jats:italic>-deficient females. At the same time, significant growth retardation, fatty liver, reduced activated levels of ribosomal S6 (S6) are seen only in <jats:italic>igf1-<\/jats:italic>deficient males. On the other hand, significant hyperglycemia, elevated transcriptional expression levels of <jats:italic>phosphenolpyruvate carboxykinase<\/jats:italic> (<jats:italic>pepck<\/jats:italic>) and levels of phosphorylated extracellular signal-regulated kinase (ERK1\/2), with additional reduced hepatic lactate\/pyruvate (L\/P) ratios can only observed in <jats:italic>igf1<\/jats:italic>-deficient females. Impaired glucose uptake has been recorded in the primary cultured hepatocytes from igf1-deficient females, but not males. Intriguingly, exposure to 17beta-estroadiol (E2) can partially ameliorated the defects of fatty liver and activation of AKT\/mTOR signaling in <jats:italic>igf1<\/jats:italic>-deficient males. Our studies demonstrate the significant functions of IGF1 on somatic regulation in zebrafish, with asymmetric gender-related consequences. Our data thus suggest that the zebrafish IGF1 is preferentially required for the activation of AKT\/mTOR signaling in male zebrafish, but glucose uptake in females.<\/jats:p>","DOI":"10.3389\/fendo.2022.879962","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T10:19:39Z","timestamp":1659089979000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Sexual dimorphic effects of igf1 deficiency on metabolism in 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