{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:16:51Z","timestamp":1787314611871,"version":"build-2736575974"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>COBLL1<\/jats:italic>\n                      gene has been implicated in human central obesity, fasting insulin levels, type 2 diabetes, and blood lipid profiles. However, its molecular mechanisms remain largely unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      In this study, we established\n                      <jats:italic>cobll1a<\/jats:italic>\n                      mutant lines using the CRISPR\/Cas9-mediated gene knockout technique. To further dissect the molecular underpinnings of\n                      <jats:italic>cobll1a<\/jats:italic>\n                      during early development, transcriptome sequencing and bioinformatics analysis was employed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Our study showed that compared to the control,\n                      <jats:italic>cobll1a<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      zebrafish embryos exhibited impaired development of digestive organs, including the liver, intestine, and pancreas, at 4 days post-fertilization (dpf). Transcriptome sequencing and bioinformatics analysis results showed that in\n                      <jats:italic>cobll1a<\/jats:italic>\n                      knockout group, the expression level of genes in the Retinoic Acid (RA) signaling pathway was affected, and the expression level of lipid metabolism-related genes (\n                      <jats:italic>fasn<\/jats:italic>\n                      ,\n                      <jats:italic>scd<\/jats:italic>\n                      ,\n                      <jats:italic>elovl2<\/jats:italic>\n                      ,\n                      <jats:italic>elovl6<\/jats:italic>\n                      ,\n                      <jats:italic>dgat1a<\/jats:italic>\n                      ,\n                      <jats:italic>srebf1<\/jats:italic>\n                      and\n                      <jats:italic>srebf2<\/jats:italic>\n                      ) were significantly changed (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01), leading to increased lipid synthesis and decreased lipid catabolism. The expression level of apolipoprotein genes (\n                      <jats:italic>apoa1a<\/jats:italic>\n                      ,\n                      <jats:italic>apoa1b<\/jats:italic>\n                      ,\n                      <jats:italic>apoa2<\/jats:italic>\n                      ,\n                      <jats:italic>apoa4a<\/jats:italic>\n                      ,\n                      <jats:italic>apoa4b<\/jats:italic>\n                      , and\n                      <jats:italic>apoea<\/jats:italic>\n                      ) genes were downregulated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Our study suggest that the loss of\n                      <jats:italic>cobll1a<\/jats:italic>\n                      resulted in disrupted RA metabolism, reduced lipoprotein expression, and abnormal lipid transport, therefore contributing to lipid accumulation and deleterious effects on early liver development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2024.1381362","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T01:08:03Z","timestamp":1713402483000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Zebrafish cobll1a regulates lipid homeostasis via the RA signaling pathway"],"prefix":"10.3389","volume":"12","author":[{"given":"Ting","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrui","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binling","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaping","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1007\/s00125-012-2756-1","article-title":"Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes","volume":"56","author":"Albrechtsen","year":"2013","journal-title":"Diabetologia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1159\/000315085","article-title":"Retinoic acid treatment enhances lipid oxidation and inhibits lipid biosynthesis capacities in the liver of mice","volume":"25","author":"Amengual","year":"2010","journal-title":"Cell. 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