Careful, fructose!
Researchers at the Zurich Higher Technical School, working under the guidance of Professor Wilhelm Krek, have deciphered a hitherto unknown molecular mechanism triggered by fructose and potentially capable of leading to cardiac hypertrophy and the development of heart failure.
In addition to the fact that fructose is part of the usual table sugar – sucrose (a disaccharide, the molecule of which consists of two monosaccharides – glucose and fructose), in its pure form it is one of the most popular sweeteners, very often included in the products lying in supermarkets on the shelves of the so-called "healthy food". Some time ago, fructose became very popular in the food industry, as it was considered less harmful than glucose. Unlike glucose, fructose practically does not increase blood glucose levels and insulin secretion. This avoids the sudden increases in insulin levels considered harmful to health in response to the consumption of a large number of sweets. In addition, fructose has a sweeter taste than sucrose.
However, later the "other side of the coin" was discovered: the liver processes fructose into fat very efficiently. Therefore, people who consume large amounts of fructose often develop obesity, high blood pressure, dyslipidemia, fatty degeneration of the liver and tissue resistance to insulin over time. The condition that includes all these symptoms is known as metabolic syndrome.
In their new study, the authors have uncovered a new, even more dangerous side effect of fructose consumption. It turned out that this carbohydrate triggers uncontrolled growth of the heart muscle, which can eventually lead to fatal heart failure.
When a person has high blood pressure, in order to ensure effective pumping of blood through the circulatory system, the heart muscle has to increase in size. The growing heart muscle needs a lot of oxygen. However, the incoming oxygen is not enough to adequately supply the growing muscle, and its cells switch to an alternative energy source. Instead of aerobic breakdown of glucose and fatty acids, they use the mechanism of glycolysis – the splitting of sugars without oxygen. If during such a period the heart muscle receives fructose in addition to glucose, this can trigger a fatal chain reaction.
The authors demonstrated that under conditions of oxygen deficiency, the presence of a HIF molecule (hypoxia-inducible factor, a factor induced by hypoxia) is registered in heart cells. This compound is a universal molecular switch that comes into play in any situation characterized by pathological growth, whether it is hypertrophy of the heart muscle or cancer. HIF triggers the production of ketohexokinase-C (KHK-C) in heart cells, the main enzyme in the fructose metabolism cycle. This enzyme has a high affinity for fructose and can break it down with high efficiency. The production of ketohexokinase-C also activates glycolysis. Since glucose metabolism does not have a mechanism of regulation through feedback, this triggers a vicious circle that can lead to the development of heart failure.
To study this mechanism, the authors used not only mouse models, but also tissue samples of patients with pathological enlargement of the heart, accompanied by a decrease in the lumen of the aortic valve, obtained during heart surgery. The cells of these samples were indeed characterized by an increased content of hypoxia-induced factor and ketohexokinase-C. In a mouse model of chronically elevated blood pressure, the researchers inactivated the enzyme ketohexokinase, which really inhibited the process of heart muscle proliferation.
Another important factor is that the body contains the enzyme ketohexokinase-A, which differs from ketohexokinase-With only a low affinity for fructose. These enzymes are encoded by the same gene, and their difference is due to alternative splicing (cutting and stitching) of information RNA (mRNA), which occurs after transcription ("translation" of the information of the corresponding gene into the sequence of RNA nucleotides). Depending on the needs of the cell, mRNA is formed on the same gene, which provides synthesis of one of the enzymes.
Under normal conditions, liver cells produce mainly ketohexokinase-C, whereas cells of other organs produce almost exclusively ketohexokinase–A. In their work, the authors showed for the first time that even an organ such as the heart, under the influence of pathogenic stress factors, is able to produce ketohexokinase-C, which is the more effective of the two enzymes. To do this, the hypoxia-induced factor activates the SF3B1 splicing factor. This molecule often has genetically determined changes in the cells of many types of cancer, which indicates a possible relationship between malignant growth and fructose.
A large amount of fructose is added to many foods and soft drinks. In the USA, due to the active use of fructose-rich corn syrup in the food industry, the consumption of fructose per capita (including infants) in the period from 1970 to 1997 increased from 230 grams to more than 28 kilograms (!) per year (per day, respectively, about 75 g, three tablespoons).
At the same time, the authors assure that the daily consumption of an adequate amount of fruit is not only safe, but also healthy. In addition to fructose, fruits contain many important trace elements, vitamins and dietary fiber. However, if possible, you should avoid the use of sugary soft drinks and juices, as well as ready-made products containing large amounts of sugar or pure fructose.
Article by Mirtschink P. et al. HIF-driven SF3B1 induces KHK-C to strengthen fructolysis and heart disease published in the journal Nature.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru
23.06.2015