Zebrafish regulates lipid homeostasis via the RA signaling pathway.

Front Cell Dev Biol

Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.

Published: April 2024

Background: The 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.

Methods: In this study, we established mutant lines using the CRISPR/Cas9-mediated gene knockout technique. To further dissect the molecular underpinnings of during early development, transcriptome sequencing and bioinformatics analysis was employed.

Results: Our study showed that compared to the control, 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 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 (, , , , , and ) were significantly changed ( < 0.01), leading to increased lipid synthesis and decreased lipid catabolism. The expression level of apolipoprotein genes (, , , , , and ) genes were downregulated.

Conclusion: Our study suggest that the loss of resulted in disrupted RA metabolism, reduced lipoprotein expression, and abnormal lipid transport, therefore contributing to lipid accumulation and deleterious effects on early liver development.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11063382PMC
http://dx.doi.org/10.3389/fcell.2024.1381362DOI Listing

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