Mechanism to protect the liver from destruction in case of obesity revealed

Scientists from the Immanuel Kant Baltic Federal University found out that blocking of receptor gp130 on the surface of liver cells helps to protect this organ from destruction in case of obesity. The matter is that fatty acids, that generated in surplus from fats, harm mitochondria – the energetic "stations" of cells – whereas IL-6 attracts special molecules, that support normal division and fusion of these cell structures. The found mechanism can be used by elaborating of drugs, that help the work of liver of people who suffer from obesity. The results of research are published in Biomedicines.

According to WHO more than 13% of Earth population suffer from obesity. This disease causes the great number of complications, connected with high load on organs. Thus, for example, people with obesity more often, than healthy people, suffer from steatosis and cirrhosis. In the first case in the cells – hepatocytes – the large amount of fat is accumulated, in the second – they are replaced by connective tissue, that is not able to fulfil the function of the healthy liver.

Accumulation of fat leads to that in the liver cells emerge a lot of reactive oxygen species, that damage molecules, including DNA, proteins and lipids of the membranes. To reduce this harmful damage help mitochondria – the energetic stations of the cell, which "utilize" damaged molecules. By this the researches show, that to sustain normal work of the mitochondria in the liver in the case of obesity helps B-cell stimulatory factor 2 – molecule exuded by cells of immune system and often participating in inflammatory reactions. B-cell stimulatory factor 2 hastens the division and fusion of mitochondria in hepatocytes, thus preserving the necessary amount of these organoids and preventing cell death. Besides this, it is well known that liver cell perceives B-cell stimulatory with the help of receptors gp130 – special "sensitive" molecules on the surface. However it is still not fully discovered, how exactly this correlation influences hepatocytes, that suffer from the surplus of fat acids in the case of obesity.

Scientists from the Immanuel Kant Baltic Federal University (Kaliningrad) artificially created conditions of obesity in the liver cell culture, by adding to them the solution of fatty acids. It turned out that already after 24 hours hepatocytes began to die. The researchers found 4 % of dead cells, whereas in the control samples, that weren't treated, almost all cells remained alive.

In the case when researches at the same time treated cells with fatty acids and B-cell stimulatory factor 2, the harmful effect lowered and the number of dead cells lessened. This effect of B-cell stimulatory factor 2 became more visible when scientists additionally treated cells with the solution, that block molecules gp130 , in that case the amount of alive cells in the culture was about 100%.

Besides this, the authors defined, that in the conditions of obesity, the genes, connected with apoptosis (programmed cell death) in hepatocytes start to work more active, and above-described observations prove it. By this the activity of about ten genes, supporting the proper work of mitochondria, lowered. When the cells were treated with fatty acid, B-cell stimulatory factor 2 and gp130, the situation changed to the contrary. This proves that these molecules support processes of division and fusion of mitochondria and by this help hepatocytes to remain alive in the condition of surplus of fatty acids.

In the experiments with cell cultures we showed that receptors gp130 help liver cells to sustain the amount and condition of mitochondria, optimal to their vital activity. This information can help by elaboration of drugs, that will improve the condition of liver of people with obesity."

Daria Skuratovskaya, First Author, Senior Researcher at the of the Centre for Immunology and Cell Biotechnology of the Immanuel Kant Baltic Federal University (Kaliningrad)

Source:
Journal reference:

Shunkina, D., et al. (2023). gp130 Activates Mitochondrial Dynamics for Hepatocyte Survival in a Model of Steatohepatitis. Biomedicines. doi.org/10.3390/biomedicines11020396.

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