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MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion

Nature Medicine volume 19, pages 892–900 (2013)Cite this article

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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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Figure 1: Effects of miR-30 family members on MTP activity and APOB secretion in Huh-7 cells.
Figure 2: Regulation of MTP mRNA by miR-30c and tissue expression pattern of miR-30c.
Figure 3: miR-30c regulates plasma and hepatic lipid concentrations.
Figure 4: miR-30c regulates hepatic lipid synthesis.
Figure 5: Effects of miR-30c in liver-specific MTP-deficient mice.
Figure 6: Effects of miR-30c on ApoB production and atherosclerosis.

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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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Authors and Affiliations

  1. School of Graduate Studies, Molecular and Cell Biology Program, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York, USA

    James Soh

  2. Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, USA

    James Soh, Jahangir Iqbal, Joyce Queiroz & M Mahmood Hussain

  3. Department of Medicine, New York University School of Medicine, New York, New York, USA

    Carlos Fernandez-Hernando

  4. Department of Cell Biology, New York University School of Medicine, New York, New York, USA

    Carlos Fernandez-Hernando

  5. Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, New York, , USA

    M Mahmood Hussain

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Contributions

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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Correspondence to M Mahmood Hussain.

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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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