How caffeine protects against cirrhosis
The protective effect of coffee for the liver was explained by DNA methylation
Daria Spasskaya, N+1
Scientists from Europe in a sample of almost 16 thousand people found a link between coffee and tea consumption and changes in DNA methylation. One of the found sites was associated with a reduced risk of developing liver obesity. The study was previously published as a preprint on bioRxiv (Karabegović et al., Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption.
Statistical studies often associate coffee consumption with certain health benefits, for example, reducing the risk of cognitive disorders, diabetes or cardiovascular diseases. A few years ago, scientists in a sample of 400 thousand people also showed that two cups of coffee a day (usually about 200 mg of caffeine) halved the risk of liver cirrhosis and death from it.
However, it is unclear how, from a biochemical point of view, coffee can mediate all these effects. It was assumed, for example, that caffeine can affect heart muscle cells through the p27 protein in mitochondria, and the combination of two components of coffee — caffeine and eicosanyl-5-hydroxytryptamide, prevents protein aggregation in neurons and, thus, can delay the development of Parkinson's disease.
Epidemiologists led by Mohsen Ghanbari from Erasmus University Rotterdam in Rotterdam (Netherlands) conducted a meta-analysis on a sample of 15,789 participants between coffee and tea consumption and the methylation status of certain sections of their DNA. It turned out that changes in the methylation of CpG dinucleotides can affect gene expression, and thereby mediate, for example, changes in lipid metabolism in the liver.
For the study, scientists participating in the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium combined several existing cohort European studies and divided their participants into two samples. The first included 9612 Europeans, and the second (replicative) included 6177 people of European and African descent. Data on dietary habits, including consumption of caffeinated beverages, and blood samples were available to all participants.
In the DNA from the blood of the study participants, the methylation status of DNA sites enriched with CpG nucleotide pairs was determined. In the composition of such pairs, cytosine (C) can be methylated in response to environmental conditions, which is often associated with a change in the expression of nearby genes. This mechanism of regulation is called epigenetic.
After that, the scientists analyzed the associations between the methylation status of known CpG sites and coffee and tea consumption. 11 coffee-dependent sites and two tea-dependent sites were found for both groups. Nine of the 11 "coffee" CpG sites were related to the genes AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH. These genes, in turn, are associated with the pathways of xenobiotic metabolism, serine biosynthesis and inflammatory response.
In addition, a search in the database of associations of methylation with gene expression led researchers to pay attention to the cg14476101 site, which turned out to be associated with a change in the expression of the PHGDH gene encoding the enzyme phosphoglycerate dehydrogenase. It has previously been shown that a change in the methylation of this site is associated with a reduced risk of liver obesity.
To test the contribution of PHGDH expression to liver function, the researchers conducted an experiment on liver cell lines and selected two with the highest and lowest levels of gene expression. It turned out that the expression of PHGDH normally correlates positively with the expression of lipid metabolism genes, and its artificial shutdown also reduces the expression of the latter.
According to the results of the experiment, the researchers suggested that coffee consumption may be associated with a reduced risk of liver diseases, such as obesity and cirrhosis, through a change in the methylation of the cg14476101 site and an indirect increase in PHGDH expression, which improves lipid metabolism. Nevertheless, the authors failed to establish a reliable cause-and-effect relationship.
Scientists have known for a long time that epigenetic changes can be caused by diet, stress, and even transmitted to offspring, but most of these studies were conducted on model animals. You can read more about this in our article "Genocide in the genome".
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