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

Abstract

Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. Overproduction of lipoproteins, a process critically 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 the MTP mRNA and induces degradation leading to reductions in its activity and media apolipoprotein B. Further, miR-30c reduces hyperlipidemia and atherosclerosis in Western diet fed mice by decreasing lipid synthesis and secretion of triglyceride-rich apoB-containing lipoproteins. Therefore, miR-30c coordinately reduces lipid biosynthesis and lipoprotein secretion to control hepatic and plasma lipids and might be useful in treating hyperlipidemias and associated disorders.

Dietary Egg Yolk Supplementation Improves Low-Protein-Diet-Induced Fatty Liver in Rats

“…Recently microRNA-30c (miR-30c) was also reported as a regulator of MTP mRNA expression (37). In Soh's study with mice (38), miR-30c did not increase hepatic TG content despite a suppression of hepatic MTP mRNA expression at the same levels as in this study (approximately 50% decrease). Therefore, low-protein-dietinduced fatty liver seems to be independent from miR30c.…”

Lipid Absorption Defects in Intestine-specific Microsomal Triglyceride Transfer Protein and ATP-binding Cassette Transporter A1-deficient Mice

“…Fatty Acid Oxidation-For fatty acid oxidation measurements, 50 mg of intestine and liver were incubated with [ 14 C]oleic acid (0.3 Ci) for 2 h, and the radiolabeled CO 2 was captured with filter paper soaked with phenylethylamine (33)(34)(35). Radiolabel was quantified using a scintillation counter (Beckman LS 6000TA).…”

microRNAs in lipoprotein and lipid metabolism: from biological function to clinical application

“…Other miRNAs are also good candidates for the treatment of dyslipidemias, including miR-30c-5p and miR-148a-3p. The overexpression of miR-30c-5p has been showed to reduce plaque formation in an atherosclerotic mouse model and, alternatively, its inhibition has induced hyperlipidemia and increased atherosclerotic plaque formation [80]. The action of miR-30c-5p was mediated by the inhibition of MTP, which regulates the secretion of VLDL by the liver, even though miR-30c-5p can also mediate its action in a MTP-independent way.…”