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Cholesterol metabolism regulation mediated by SREBP-2, LXRα and miR-33a in rainbow trout (Oncorhynchus mykiss) both in vivo and in vitro

Abstract : Cholesterol metabolism is greatly affected in fish fed plant-based diet. The regulation of cholesterol metabolism is mediated by both transcriptional factors such as sterol regulatory element binding proteins (SREBPs) and liver X receptors (LXRs), and posttranscriptional factors including miRNAs. In mammals, SREBP-2 and LXRα are involved in the transcrip-tional regulation of cholesterol synthesis and elimination, respectively. In mammals, miR-33a is reported to directly target genes involved in cholesterol catabolism. The present study aims to investigate the regulation of cholesterol metabolism by SREBP-2 and LXRα and miR-33a in rainbow trout using in vivo and in vitro approaches. In vivo, juvenile rainbow trout of~72 g initial body weight were fed a total plant-based diet (V) or a marine diet (M) containing fishmeal and fish oil. In vitro, primary cell culture hepatocytes were stimulated by graded concentrations of 25-hydroxycholesterol (25-HC). The hepatic expression of cholesterol synthetic genes, srebp-2 and miR-33a as well as miR-33a level in plasma were increased in fish fed the plant-based diet, reversely, their expression in hepatocytes were inhibited with the increasing 25-HC in vitro. However, lxrα was not affected neither in vivo nor in vitro. Our results suggest that SREBP-2 and miR-33a synergistically enhance the expression of cholesterol synthetic genes but do not support the involvement of LXRα in the regulation of cholesterol elimination. As plasma level of miR-33a appears as potential indicator of cholesterol synthetic capacities, this study also highlights circulating miRNAs as promising noninvasive biomarker in aquaculture.
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https://hal.inrae.fr/hal-02860733
Déposant : Pascale Avril <>
Soumis le : lundi 8 juin 2020 - 15:18:09
Dernière modification le : vendredi 3 juillet 2020 - 12:14:03

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Tengfei Zhu, Geneviève Corraze, Elisabeth Plagnes-Juan, Sandrine Skiba-Cassy. Cholesterol metabolism regulation mediated by SREBP-2, LXRα and miR-33a in rainbow trout (Oncorhynchus mykiss) both in vivo and in vitro. PLoS ONE, Public Library of Science, 2020, 15 (2), ⟨10.1371/journal.pone.0223813⟩. ⟨hal-02860733⟩

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