They identify a mechanism that can predispose us to suffer metabolic diseases

The human genome encodes a large number of genes (about 30,000), many of them with still unknown functions. Understanding the function of each of these genes is essential to know what diseases arise when these genes fail.

A new study has shown in mice that the absence of the Tet3 gene alters the metabolism of the organism’s differentiated cells. This is because they are not capable of generating energy through the usual mechanisms, initiating an alternative and abnormal process observed in certain metabolic diseases such as cancer and diabetes. The results of the study will help identify unique processes that can give rise to metabolic diseases, something essential for early diagnosis and effective treatment.

The study has been carried out by an international team that includes Natalia Tapia and Isabel Mulet, both from the Institute of Biomedicine of Valencia (IBV), attached to the Higher Council for Scientific Research (CSIC), both institutions in Spain. The group of Marcos J. Araúzo-Bravo, from the Biogipuzkoa Health Research Institute, also participated in the study; and that of Carsten Hopf, from the University of Applied Sciences of Mannheim (Germany), among others.

It has been observed that a malfunction of the Tet3 gene occurs in many types of metabolic diseases such as diabetes or obesity, as well as in several types of cancer.

To do this, the research team deleted the Tet3 gene in transgenic mice and then studied the consequences of its absence. “A large majority of tissues contain stem cells, also called stem cells, which differentiate giving rise to all the cells that make up a tissue,” explains Tapia. “While stem cells obtain their energy mainly from glycolytic metabolism, differentiated cells do so from a metabolism based on oxidative phosphorylation,” describes the CSIC researcher.

Oxidative phosphorylation is a mechanism that differentiated cells use to generate large amounts of energy, which is carried out entirely within the mitochondria. On the other hand, there is another mechanism that does not require the use of mitochondria, but is less energy efficient, called glycolysis. The preferential use of glycolysis over oxidative phosphorylation in differentiated cells leads to the appearance of metabolic alterations.

Longitudinal section of the intestine in which a villus of the intestinal epithelium has been outlined in red, a tissue in which the expression pattern of the Tet3 gene has been studied. (Image: IBV / CSIC)

“Our results demonstrate that the differentiated cells of the mouse organism present alterations in the absence of the Tet3 gene and are not capable of carrying out oxidative phosphorylation efficiently, which is why they maintain glycolytic metabolism at higher levels than normal, a phenomenon that It has also been observed in many types of tumor cells,” reveals Tapia.

“Our study suggests that the loss of function of the Tet3 gene forces cells towards an aberrant metabolic state, which can promote the appearance of certain diseases such as cancer,” summarizes Tapia.

The study is titled “TET3 regulates terminal cell differentiation at the metabolic level.” And it has been published in the academic journal Nature Communications. (Source: Isidoro García / CSIC)