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Plant microRNAs found in humans who eat them

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  • Plant microRNAs found in humans who eat them

    MicroRNAs are small snippets of RNA that are crucial in regulating gene expression. The idea that plant microRNA consumed by humans could end up regulating their metabolism is very surprising, at least to me.

    The work here doesn't prove the hypothesis but shows that plant miRNA are present in tissue in very significant quantities, two of which could regulate cholesterol metabolism. I suspect that lots of labs will be double checking this work very carefully. The implications are enormous.

    Plant RNAs Found in Mammals

    MicroRNAs from plants accumulate in mammalian blood and tissues, where they can regulate gene expression.

    By Cristina Luiggi | September 20, 2011
    17 Comments
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    MicroRNAs from common plant crops such as rice and cabbage can be found in the blood and tissues of humans and other plant-eating mammals, according to a study published today in Cell Research. One microRNA in particular, MIR168a, which is highly enriched in rice, was found to inhibit a protein that helps removes low-density lipoprotein (LDL) from the blood, suggesting that microRNAs can influence gene expression across kingdoms.

    “This is a very exciting piece of work that suggests that the food we eat may directly regulate gene expression in our bodies,” said Clay Marsh, Director of the Center for Personalized Health Care at the Ohio State University College of Medicine who researches microRNA expression in human blood but who was not involved in the study.

    MicroRNAs are, as the name implies, very short RNA sequences (approximately 22 nucleotides in length) discovered in the early 1990s. They are known to modulate gene expression by binding to mRNA, often resulting in inhibition. With the recent discovery that microRNAs circulate the blood by hitching a ride in small membrane-encased particles known as microvesicles (see our July 2011 feature on microvesicles, “Exosome Explosion”), there has been a surge of interest in microRNAs as a novel class of biomarkers for a variety of diseases.

    Chen-Yu Zhang, a molecular biologist at Nanjing University in China, was studying the role of circulating microRNAs in health and disease when he discovered that microRNAs are present in other bodily fluids such as milk. This gave him the “crazy idea” that exogenous microRNAs, such as those ingested through the consumption of milk, could also be found circulating in the serum of mammals, he recalled.

    To test his hypothesis, Zhang and his team of researchers sequenced the blood microRNAs of 31 healthy Chinese subjects and searched for the presence of plant microRNAs. Because plant microRNAs are structurally different from those of mammals, they react differently to oxidizing agents, and the researchers were able to differentiate the two by treating them with sodium periodate, which oxidizes mammal but not plant microRNAs.

    To their surprise, they found about 40 types of plant microRNAs circulating in the subjects’ blood—some of which were found in concentrations that were comparable to major endogenous human microRNAs.

    The plant microRNAs with the highest concentrations were MIR156a and MIR168a, both of which are known to be enriched in rice and cruciferous vegetables such as cauliflower, cabbage, and broccoli. Furthermore, the researchers detected the two microRNAs in the blood, lungs, small intestine, and livers of mice, in variable concentrations that significantly increased after the mice were fed raw rice (although cooked rice was also shown to contain intact MIR168a).

    Next, the researchers scoured sequence databases for putative target genes of MIR156a and MIR168a and found that MIR168a shared sequence complementarity with approximately 50 mammalian genes. The most highly conserved of these sequences across the animal kingdom was the exon 4 of the low-density lipoprotein receptor adapter protein 1 gene (LDLRAP1).

    LDLRAP1 is highly expressed in the liver, where it interacts with the low-density lipoprotein receptor to help remove low-density lipoprotein (LDL), aka “bad” cholesterol, from the blood.

    The researchers hypothesized that MIR168a could be taken up by the epithelial cells lining the gastrointestinal tract, packaged into microvesicles, and secreted into the blood stream, where they can make their way to target organs. Once in the liver, MIR168a binds to LDLRAP1 mRNA, reducing the protein levels and ultimately impairing the removal of LDL from the blood.

    To test this hypothesis in vitro, the researchers transfected synthetic MIR168a into a human epithelial cell line and collected the secreted microvesicles. When they added these microvesicles to a liver cell line called HepG2, they found that while it did not change the levels of LDLRAP1 mRNA, it did decrease the levels of the actual LDLRAP1 protein.

    Likewise, the LDLRAP1 protein level decreased in the livers of live mice 3 to 7 days after eating fresh rice or being injected with synthetic MIR168a—significantly increasing LDL in the blood. When the researchers injected the mice with an RNA sequence that bound to and neutralized MIR168a, the protein and LDL levels returned to normal.

    “This microRNA inhibits this protein and increased the plasma LDL levels,” Zhang said. With higher levels of circulating cholesterol, “it can possibly increase the risk of metabolic syndrome,” he added. But more importantly, this research points to a “new therapeutic strategy for the treatment of diseases,” based on the enhancement or inhibition of exogenous microRNAs.

    Although the team has still a long way to go in elucidating the mechanisms by which plant microRNAs can regulate gene expression in humans, these initial results promise to increase the understanding of how specific ingredients in food can mediate health and disease, Marsh said.

    Indeed, Zhang suspects that this is just one example of many. With time, “I’m confident other people will find more exogenous plant microRNAs that can pass through the GI tract and also have effects on the host physiology,” Zhang said.

    L. Zhang, et. al., “Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA,” Cell Research, doi:10.1038/cr.2011.158, 2011.
    Last edited by citanon; 21 Sep 11,, 02:09.

  • #2
    If true, does that mean eating too much rice may also increase cholesterol?
    "Only Nixon can go to China." -- Old Vulcan proverb.

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    • #3
      Originally posted by gunnut View Post
      If true, does that mean eating too much rice may also increase cholesterol?
      Wasn't rice rich with fibers, therefor good for the heart and bad for the cholesterol?
      No such thing as a good tax - Churchill

      To make mistakes is human. To blame someone else for your mistake, is strategic.

      Comment


      • #4
        Originally posted by Doktor View Post
        Wasn't rice rich with fibers, therefor good for the heart and bad for the cholesterol?
        There's a study out every other week that refutes the last study.

        Caffine is good. Caffine is bad.

        Eggs are good. Eggs are bad.

        Wine is good. Wine is bad.

        I still believe in moderation. I eat everything I want. I just don't over eat. I drink, but I don't get drunk. I eat junk food, but not a lot.
        "Only Nixon can go to China." -- Old Vulcan proverb.

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        • #5
          Moderation is everything. When I was a kid my parents thought me not to overdo anything. Their perfect example was honey. While everyone will tell you it's good, try eating 20 oz in one hour ;)
          No such thing as a good tax - Churchill

          To make mistakes is human. To blame someone else for your mistake, is strategic.

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          • #6
            There are lots of questionable findings here. We will have to wait to see how this all shakes out.

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            • #7
              That's.....that's.....no. Nuh-uh. Nawwwww... So very much is wrong with this...

              Frankly, I don't believe it. I suppose I should read the paper before being so dismissive, but...but...it just don't make sense.
              I enjoy being wrong too much to change my mind.

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              • #8
                Moderation, and variation.
                "Football is war."

                -Rinus Michels

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                • #9
                  Sounds like a VERY fancy way of saying that vegetables are good for you. Duh.

                  Now please direct me to the study that proves donuts are good for me. :)
                  Don't listen to me, I'm a wack job.

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                  • #10
                    Originally posted by Laser View Post
                    Sounds like a VERY fancy way of saying that vegetables are good for you. Duh.

                    Now please direct me to the study that proves donuts are good for me. :)
                    Whit which fill?
                    No such thing as a good tax - Churchill

                    To make mistakes is human. To blame someone else for your mistake, is strategic.

                    Comment


                    • #11
                      Originally posted by Doktor View Post
                      Moderation is everything.
                      Moderation is for monks

                      -Heinlein
                      "We will go through our federal budget – page by page, line by line – eliminating those programs we don’t need, and insisting that those we do operate in a sensible cost-effective way." -President Barack Obama 11/25/2008

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                      • #12
                        Originally posted by gunnut View Post
                        There's a study out every other week that refutes the last study.

                        Caffine is good. Caffine is bad.

                        Eggs are good. Eggs are bad.

                        Wine is good. Wine is bad.

                        I still believe in moderation. I eat everything I want. I just don't over eat. I drink, but I don't get drunk. I eat junk food, but not a lot.
                        And so you'll live long, but not very long.

                        Comment


                        • #13
                          Originally posted by citanon View Post
                          And so you'll live long, but not very long.
                          To put it in other words, moderately long
                          No such thing as a good tax - Churchill

                          To make mistakes is human. To blame someone else for your mistake, is strategic.

                          Comment


                          • #14
                            Originally posted by Doktor View Post
                            To put it in other words, moderately long
                            I recall a movie where a charactor mentioned he was not very old in terms of a mountain - but was very old in terms of a peach...
                            sigpic"If your plan is for one year, plant rice. If your plan is for ten years, plant trees.
                            If your plan is for one hundred years, educate children."

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                            • #15
                              Originally posted by Laser View Post
                              Sounds like a VERY fancy way of saying that vegetables are good for you. Duh.

                              Now please direct me to the study that proves donuts are good for me. :)
                              Throw a veggi on that doughnut. My dessert is always healthy....when I put a banana on my 3 scoop sundae.....Ok 4 scoops........almost never 5............
                              Removing a single turd from the cesspool doesn't make any difference.

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