Saturday, 26 May 2012

We Are What We Eat: How Consuming Greens Affects Our Genes

Fig 1. MicroRNA formation and function

With the latest advances in genetics, the age-old adage “you are what you eat” becomes reality. 

Recent studies suggest that genetic material of plant foods are capable of surviving digestion and subsequently circulating throughout host bodies to regulate physiology. Specifically, a novel study by Chen-Yu Zhang at the University of Nanjing found that orally ingested exogenous plant microRNAs are present in the sera and tissues of mammals and actively function to manipulate gene expression. 

MicroRNA are small non-coding RNA molecules between 19 and 24 nucleotides long, produced from a hairpin structure on a precursor RNA molecule. By binding to messenger RNA (mRNA) molecules, microRNA molecules degrade mRNA or prevent the action of enzymes involved in the translation of mRNA into proteins, thus silencing the expression of associated genes.

For this study, blood samples of 31 Chinese subjects were analysed with a treatment of the oxidating agent sodium periodate. This prevented the transcription of mammal microRNA while allowing the amplification of plant microRNA, which are periodate resistant due to the 2’-O-methylated on the terminal nucleotide. Of the 30 known plant microRNAs identified in the bloodstream of samples, MIR168a and MIR156a – abundant in rice (Oryza sativa) and cruciferous vegetables (Brassicaceae family) respectively – were present in especially high concentrations. 
Fig 2. MIR168a found in rice
Fig 3. MIR156a found in members of Brassicaceae family

In vitro and in vivo analyses of mice demonstrated that plant microRNAs passed through the gastrointestinal track and entered the circulation of organs such as the liver, small intestines and lungs. It was also noted that 168a and 156a levels in the sera and tissues of mice fed a diet of fresh rice were 5-10 times higher than in mice assigned a low fat and cholesterol diet. Thus it was hypothesised that microRNA present in human blood samples originated from food and survive digestion to circulate through the body.

Fig 4. MIR168a structure
Further experiments were conducted to test the functional ability of plant microRNA in animal blood. Through a bioinformatics analysis, 50 mammal genes with sequences complementary to MIR168a were identified, including low-density lipoprotein receptor adoprotein 1 (LDLRAP1). LDLRAP1 is abundant in in the liver where it functions to remove low-density lipoprotein or bad cholesterol from the bloodstream. This was supported by a preliminary experiment in which packages of MIR168a added to mammalian liver cells inhibited LDRAP1 production. It was then found through a comparative study of mice fed chow diets and rice diets, that higher levels of MIR168a inhibited the expression of LDLRAP1 in the liver of mice, thus increased the plasma cholesterol level of rice-fed mice.  Therefore, plant microRNA was observed to raise levels of LDL in mice.

The findings of Zhang’s study suggest that plant microRNA are capable of cross-kingdom activity and may be newly classified as a universal moderator or functional component of food, similar to vitamins, essential nutrients and minerals. The properties of exogenous plant microRNA outlined in this study have strong implications for the future role of genetics in nutrition and health studies, such the development of diets and plants with medicinal effects.



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