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Tiny RNA Has Big Effects on Lipid Metabolism and Atherosclerosis

Scientists have shown that a small molecule, called “microRNA,” plays a big role in lipid (fat) metabolism and related health conditions such as hyperlipidemia (elevated lipid levels in the blood) and atherosclerosis (clogging and hardening of the arteries). High levels of lipids circulating in the blood put individuals at higher risk for cardiovascular and metabolic disorders. Lipids are carried in the blood in packages called lipoproteins, which are assembled, mostly in the liver, with help from proteins such as the microsomal triglyceride transfer protein, or MTP. Researchers aimed to determine whether there were any regulators of MTP in the body that might be targets for lowering elevated blood lipids. MicroRNAs or “miRNAs” are small pieces of RNA that target another type of RNA, abbreviated mRNA (for messenger RNA), which is involved in protein production—ultimately, reducing the amount of protein made from the mRNA.

The research team looked at several miRNAs thatcould potentially regulate MTP and identiied one—miR-30c—that reduced MTP activity, as well as decreased the concentration of lipoproteins secreted in a cell culture model. They found that miR-30c accomplishes this feat by binding to and degrading MTP mRNA. To test the miRNA’s effects on physiological functions, they moved to an animal model—mice that were injected with a substance to boost miR-30c levels in the liver, in particular. After three weeks, the mice had reduced levels of MTP in the liver, as well as cholesterol in the blood, reflecting that amounts of certain lipoproteins were also lowered. Surprisingly, the abundance of miR-30c not only inhibited the packaging of lipids into lipoproteins, but it also inhibited the synthesis of the lipids themselves, suggesting an even greater role for this miRNA in lipid metabolism. Mice with extra miR-30c in the liver also had fewer, smaller plaques in their arteries; large amounts of arterial plaques are a sign of atherosclerosis. The results of this study outline the key role of this speciic miRNA in reducing lipid synthesis, secretion of speciic lipoproteins, and, ultimately, atherosclerosis. These indings highlight the potential importance of agents that could boost or mimic the effects of this miRNA as a treatment for those at risk for cardiovascular and metabolic disorders.


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