Abstract
Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. Overproduction of lipoproteins, a process that is dependent on microsomal triglyceride transfer protein (MTP), can contribute to hyperlipidemia. We show that microRNA-30c (miR-30c) interacts with the 3′ untranslated region of MTP mRNA and induces its degradation, leading to reductions in MTP activity and in apolipoprotein B (APOB) secretion. miR-30c also reduces lipid synthesis independently of MTP. Hepatic overexpression of miR-30c reduced hyperlipidemia in Western diet–fed mice by decreasing lipid synthesis and the secretion of triglyceride-rich ApoB-containing lipoproteins and decreased atherosclerosis in Apoe−/− mice. Furthermore, inhibition of hepatic miR-30c by anti–miR-30c increased hyperlipidemia and atherosclerosis. Therefore, miR-30c coordinately reduces lipid biosynthesis and lipoprotein secretion, thereby regulating hepatic and plasma lipid concentrations. Raising miR-30c levels might be useful in treating hyperlipidemias and associated disorders.
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20 September 2013
In the version of this article initially published, the text incorrectly described the results of previously published studies of miR-30 family members. This sentence has now been corrected to read as follows: “miR-30a has a role in Xenopus kidney development26, miR-30e regulates apoptosis in breast tumor cells27, and miR-30a, miR-30c and miR-30d stimulate adipogenesis28,29.” The error has been corrected for the PDF and HTML versions of this article.
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Acknowledgements
This work was supported in part by US National Institutes of Health grants DK-46900 and HL-95924 to M.M.H. Mttpflox/flox mice were from L. Chan (Baylor University).
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J.S. performed all the experiments, analyzed data and wrote a draft of the paper. J.I. taught J.S. different techniques, participated in atherosclerosis experiments and edited figures. J.Q. performed sectioning and staining of aortas. C.F.-H. discussed experiments and edited the manuscript. M.M.H. conceived the ideas, designed and discussed experiments, supervised progress and extensively edited and communicated regarding the manuscript.
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Soh, J., Iqbal, J., Queiroz, J. et al. MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion. Nat Med 19, 892–900 (2013). https://doi.org/10.1038/nm.3200
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DOI: https://doi.org/10.1038/nm.3200
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