Carboxyl ester lipase (Cel), is a lipolytic enzyme secreted by the pancreas, which hydrolyzes various species of lipids in the gut. Cel is also secreted by mammary gland during lactation and exists in breast milk. It facilitates dietary fat digestion and absorption, thus contributing to normal infant development. This study aimed to examine whether the Cel in zebrafish embryos has a similar role of maternal lipid utilization as in human infants, and how Cel contributes to the utilization of yolk lipids in zebrafish. The cel1 and cel2 genes were expressed ubiquitously in the blastodisc and yolk syncytial layer before 24 hpf, and in the exocrine pancreas after 72 hpf. The cel1 and cel2 morphants exhibited developmental retardation and yolk sac retention. The total cholesterol, cholesterol ester, free cholesterol, and triglyceride were reduced in the morphants' body while accumulated in the yolk (except triglyceride). The FFA content of whole embryos was much lower in morphants than in standard controls. Moreover, the delayed development in cel (cel1/cel2) double morphants was partially rescued by FFA and cholesterol supplementation. Delayed and weakened cholesterol ester transport to the brain and eyes was observed in cel morphants. Correspondingly, shrunken midbrain tectum, microphthalmia, pigmentation-delayed eyes as well as down-regulated Shh target genes were observed in the CNS of double morphants. Interestingly, cholesterol injections reversed these CNS alterations. Our findings suggested that cel genes participate in the lipid releasing from yolk sac to developing body, thereby contributing to the normal growth rate and CNS development in zebrafish.

中文翻译：

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在斑马鱼和人的早期发育过程中，羧基酯脂肪酶在利用母体提供的脂质方面高度保守。

羧基酯脂肪酶（Cel）是胰腺分泌的脂解酶，可水解肠道中的各种脂质。乳汁在哺乳期间也会被乳腺分泌，并存在于母乳中。它有助于饮食中脂肪的消化和吸收，从而有助于婴儿的正常发育。这项研究旨在检查斑马鱼胚胎中的Cel是否具有与人类婴儿相似的母体脂质利用作用，以及Cel如何促进斑马鱼卵黄脂质的利用。cel1和cel2基因在24 hpf之前在胚盘和卵黄合胞体层中普遍表达，在72 hpf之后在外分泌胰腺中普遍表达。cel1和cel2 morphant表现出发育迟缓和卵黄囊保留。总胆固醇，胆固醇酯，游离胆固醇 甘油三酸酯和甘油三酸酯在吗啡体内减少，而在蛋黄中积累（甘油三酸酯除外）。与标准对照相比，吗啡中全胚的FFA含量要低得多。此外，通过FFA和胆固醇补充可以部分缓解cel（cel1 / cel2）双吗啡的延迟发育。在cel morphant中观察到胆固醇酯向大脑和眼睛的运输延迟和减弱。相应地，在双吗啡的中枢神经系统中观察到收缩的中脑盖，小眼，色素沉着延迟的眼睛以及Shh靶基因的下调。有趣的是，胆固醇注射逆转了这些CNS改变。我们的发现表明cel基因参与了从卵黄囊向发育中体的脂质释放，