Obesity is a disease that has become an important public health issue as well as a risk factor for diseases such as type 2 diabetes, cardiovascular disease and some forms of cancer.
Although it is traditionally thought to be due to an imbalance between intake and energy consumption that favors fat storage, it is already recognized that interactions between environmental and genetic factors (Epidemiology) play a key role in its development,
Researchers from the Center for Biomedical Research in the Diabetes Network and Related Metabolic Diseases (Ciberdem) from the group led by John Wendell and Sonia Fernandez-Veledo at the San Diego Institute of Sanitary Studies Pere Virgili (Catalonia, Spain) Another step in the knowledge of the processes , which trigger these interactions between the gene and the environment.
Experts identify a new mechanism by which obesity leaves an epigenetic footprint on adipocyte precursor cells that defines the damage of new fat cells that are generated.
Previous studies in the same group have already shown that adipocyte precursor cells in obese patients do not work properly. So far, however, the molecular basis of these changes has not been known.
"Subcutaneous fat of obese subjects contains a non-functional set of adipocyte precursor stem cells and there is evidence of a link between obesity and the loss of function of these stem cells," explains Sonia Fernández Veledo, the last signatory to the study, which will be published in the International Journal of Obesity.
Adequate functional population of adipocyte precursors is crucial for the proper fat expansion, lipid management and prevention of lipotoxicity in the face of chronic positive energy balance (ie, when all ingested calories are not "burned"). ,
"We believe that a better understanding of the biology of this set of precursor stem cells can contribute to the development of new strategies designed to combat obesity or stimulate the growth of healthy fat tissues," the expert added.
For this purpose, this new work has examined stem cells derived from fatty tissue (precursors) and mature adipocytes in healthy thin and obese patients.
"Our work shows that obesity leads to important epigenetic changes in precursor cell DNA, which determines the malfunction of the new adipocytes that are generated," says John Vendler, leader of the Ciberdem group at IISPV.
"Obesity determines adipocyte precursor stem cells with a dynamic loss of methylation of DNA in selected areas, which can ultimately cause white fat dysfunction and the development of metabolic obesity syndromes," he explains.
One of the most modified genes is the transcription factor TBX15, a factor involved in adipogenesis, fat distribution, and brown (the transformation of white fat into brown fat, the latter being healthy and necessary to the body)
The study showed that TBX15 is one of the genes with the most changes in the epigenetic level in obese precursor cells, which means they are overexpressed in these cells. "TBX15 shows a strong loss of epigenetic markers with a corresponding increase in the level of gene and protein expression," they explain.
The work has found that TBX15 is a regulator of mitochondrial mass in obese adipocytes, a major organel in the metabolism of cells responsible for cellular respiration. "Increasing TBX15 in the fat tissue of obese patients leads to a change in the mitochondrial network, resulting in changes in shape and number," the researchers added.
This new human study demonstrates the importance of changing the epigenetic signs due to obesity in the functionality of future adipocytes, supporting the theory of precursor dysfunction as a key event in this disease.
"We are currently exploring whether this epigenetic footprint is reversible, ie if weight loss can reverse the epigenetic changes caused by obesity," says John Wendel.