Scholarlink

<p>To evaluate the significance of bile salt-activated lipase (BSAL) in lipid digestion and metabolism in fish, this study used CRISPR/Cas9 gene editing to generate medaka (<i>Oryzias latipes</i>) <i>bsal</i> mutant lines. Given that the <i>bsal</i> gene comprises three copies (<i>bsal</i>, <i>cel.2</i>, and <i>bsal-like</i>) in the medaka genome, <i>bsal-like</i> variants may lead to functional loss in lipid hydrolysis owing to amino acid residue alterations in the bile salt binding site. Consequently, two types of medaka mutants, <i>bsal</i><sup><i>−/−</i></sup> and <i>bsal</i><sup><i>−/−</i></sup><i>/cel.2</i><sup><i>−/−</i></sup>, were generated for experimental exploration in this study. Compared to wild-type (WT) medaka, the <i>bsal⁻/⁻/cel.2⁻/⁻</i> group showed significant reductions in body length, expression of growth-related genes (<i>gh</i> and <i>igf</i>), total lipase and protease activities, and body composition (cholesterol, triglyceride, and protein levels). The <i>bsal⁻/⁻/cel.2⁻/⁻</i> group also exhibited upregulated expression of lipid synthesis genes (<i>fas</i>, <i>acc1</i>, <i>scd</i>) and downregulated expression of lipolysis-related genes (<i>cpt1</i>, <i>acox1</i>). Notably, key glycolysis genes (<i>pk</i>, <i>gk</i>) and gluconeogenesis-related genes (<i>pck2</i>) were significantly upregulated in the <i>bsal⁻/⁻/cel.2⁻/⁻</i> group. However, the <i>bsal</i><sup><i>−/−</i></sup> group exhibited no significant differences from the WT group in all assays, except for notable reductions in protease activity and expression levels of the <i>cpt1</i> and <i>gk</i> genes, as well as a significant increase in <i>pck2</i> gene expression compared to the WT group. Remarkably, the expression level of the <i>cel.2</i> gene was significantly elevated in the <i>bsal</i><sup><i>−/−</i></sup> group compared to the WT group. In summary, this study demonstrates the pivotal role of the <i>bsal</i> gene in lipid digestion and metabolism in medaka. Furthermore, the presence of multiple copies of the <i>bsal</i> gene aids in fulfilling the demands of lipid digestion in medaka. This conclusion can provide insights into the research on lipid digestion and metabolism in other fish species. </p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Knockout of bsal/cel.2 results in growth retardation, reduced lipid digestion and altered energy metabolism in medaka larvae (oryzias latipes)

  • 期刊论文

  • 发表日期：

    2026年5月14日

查看全文
  • Ruipeng Xie,
  • Chenyuan Zhu,
  • Xufang Liang,
  • Ke Lu,
  • Jiaqi Wu

摘要

To evaluate the significance of bile salt-activated lipase (BSAL) in lipid digestion and metabolism in fish, this study used CRISPR/Cas9 gene editing to generate medaka (Oryzias latipes) bsal mutant lines. Given that the bsal gene comprises three copies (bsal, cel.2, and bsal-like) in the medaka genome, bsal-like variants may lead to functional loss in lipid hydrolysis owing to amino acid residue alterations in the bile salt binding site. Consequently, two types of medaka mutants, bsal−/− and bsal−/−/cel.2−/−, were generated for experimental exploration in this study. Compared to wild-type (WT) medaka, the bsal⁻/⁻/cel.2⁻/⁻ group showed significant reductions in body length, expression of growth-related genes (gh and igf), total lipase and protease activities, and body composition (cholesterol, triglyceride, and protein levels). The bsal⁻/⁻/cel.2⁻/⁻ group also exhibited upregulated expression of lipid synthesis genes (fas, acc1, scd) and downregulated expression of lipolysis-related genes (cpt1, acox1). Notably, key glycolysis genes (pk, gk) and gluconeogenesis-related genes (pck2) were significantly upregulated in the bsal⁻/⁻/cel.2⁻/⁻ group. However, the bsal−/− group exhibited no significant differences from the WT group in all assays, except for notable reductions in protease activity and expression levels of the cpt1 and gk genes, as well as a significant increase in pck2 gene expression compared to the WT group. Remarkably, the expression level of the cel.2 gene was significantly elevated in the bsal−/− group compared to the WT group. In summary, this study demonstrates the pivotal role of the bsal gene in lipid digestion and metabolism in medaka. Furthermore, the presence of multiple copies of the bsal gene aids in fulfilling the demands of lipid digestion in medaka. This conclusion can provide insights into the research on lipid digestion and metabolism in other fish species.