Liver regulates lipid, carbohydrate and protein metabolism. It also segregates a number of proteins and enzymes, and eliminates toxic substances from the organism. Liver regeneration is a mostly unknown process at a molecular level, although it is essential for the good functioning of the liver, and indispensable in order to carry out some therapeutic strategies, such as living-donor transplant. The journal Science publishes in its last issue a research article where researchers from IDIBAPS, in collaboration with Universitat de Barcelona (UB) and Queensland University (Australia) discover the importance of caveolin-1 in liver regeneration. Without this protein, regeneration does not occur. This research work has been directed by Dr. Albert Pol, one of the first researchers with a Ramón y Cajal contract; and Dr. Carles Enrich, from the Department of Cell Biology and Pathological Anatomy from the Faculty of Medicine of the UB. The first signatories of this article are Manuel A. Fernández and Cecilia Albor.
Stem cells do not participate in liver regeneration, but hepatocytes, cells of the liver tissue, are able to regain their division capacity when needed. In a normal liver, hepatocytes do not divide, but during regeneration, all liver cells duplicate at least once. For this system to function, a fine regulation system is needed, permitting the hepatocyte to accumulate energetic reserves in the form of lipid accumulations, and starting the genetic machinery for division. IDIBAPS researchers studied the role of caveolin-1 in this process, comparing the regenerative capacity of normal mice and modified mice, which do not express the caveolin-1 gene. Both types of mice were extirpated 70% of their liver mass, and differences in regeneration process were analysed through microscopic and molecular techniques.
During the first stages of regeneration, liver cells accumulate a large amount of lipids in structures called lipidic bodies, whose importance was until today unknown. This study published in Science demonstrates that the energy needed in liver regeneration comes from lipids accumulated in liver cells during the first hours of the process. Genetically modified mice, not expressing caveolin-1, were incapable of forming the lipidic bodies necessary in order to provide energy for the regeneration. After 48 hours of the extraction of a part of the liver, the mortality of modified mice increased, and, after 72 hours, only 22% survived, whereas normal mice survived in 89% of cases. Similar results were obtained by avoiding caveolin-1 expression with the interference RNA technique, and the administration of glucose in mice without caveolin allowed them to have an alternative energy source and were able to regenerate liver with more normality.
Summarising, this work makes two important contributions: On the one hand, it reveals the main vital function of lipid bodies and caveolin. This is a protein linked to the storage of lipids and cell cycle, but a situation where its presence is indispensable for the survival of experimental animals has been described in this study for the first time. On the other hand, the article published in Science demonstrates that lipids can be the fuel for cell division, whereas until today, it was assumed that glucose was its first energy source. This discovery could explain why steatosis, a disease where an excessive accumulation of lipids in the liver, is considered a risk factor for the apparition of hepatocellular tumours. The excessive accumulation of lipids in the hepatocyte, as a consequence of excessive consumption of nutrients, obesity, type-2 diabetes or due to a bad liver functioning, affects in several degrees up to two thirds of the population in developed countries. Our researchers claim that an excess of lipid could represent for these cells an energy source sufficient to proliferate inadequately and, thus, to develop hepatic tumours.
Journal
Science