Monday , January 18 2021

Why Obesity Changes Adipocyte Function – Digital AIM



Obesity is a disease that has become an important public health problem, as well as a risk factor for diseases such as type 2 diabetes, cardiovascular diseases and some forms of cancer.

This study, conducted in humans, has shown the importance of changing epigenetic marks due to obesity. (Photo: Pixabay)

Although traditionally it is believed that this is due to an imbalance between energy consumption and consumption, which contributes to the storage of fat, it is now recognized that the interaction between environmental and genetic factors (the so-called epigenetics) plays a key role in its development,

Researchers at the Center for Biomedical Research on Diabetes and Related Metabolic Diseases (Ciberdem) from a group led by Joan Wendrell and Sonja Fernandez-Veledo at the Sanitary Research Institute. Peru Virgil (IISPV) (Catalonia, Spain), just given Another step in understanding the processes that cause these interactions of genes and the environment.

Experts have identified a new mechanism in which obesity leaves an epigenetic imprint on the precursor cells of adipocytes, which determines the malfunction of new fat cells that are generated.

Previous studies from the same group have already shown that adipocyte progenitor cells in patients with obesity do not work correctly. However, to date, the molecular basis of these changes is unknown.

"The fatty subcutaneous adipose tissue contains a dysfunctional set of adipocyte progenitor stem cells, and there is evidence of an association between obesity and loss of function of these stem cells," explains Sonja Fernandez Veledo, the last participant in the study, which ends for publication in the International Journal of Obesity.

Adequate functional population of adipocyte precursors is crucial for proper fat expansion, lipid management and lipotoxicity prevention under conditions of chronic positive energy balance (that is, when all calories consumed are not “burned”). ,

“We believe that a better understanding of the biology of this set of progenitor stem cells can contribute to the development of new strategies to combat obesity or promote the expansion of healthy adipose tissue,” the expert adds.

For this purpose, stem cells derived from adipose tissue (precursors) and mature adipocytes of healthy patients suffering from thin and obese have been studied in this new work.

“Our work shows that obesity causes important epigenetic changes in the DNA of progenitor cells, which determines the malfunctioning of new adipocytes that are generated,” says Joan Vendrell, leader of the Ciberdem group at IISPV.

"Obesity causes adipocyte progenitor stem cells with a dynamic loss of DNA methylation in certain regions, which may ultimately cause dysfunction of white adipose tissue and the development of metabolic syndromes in obesity," he explains.

One of the most modified genes is the transcription factor TBX15, a factor associated with adipogenesis, fat distribution and toasting (the conversion of white fat to brown fat, the last healthy and necessary for the body),

The study showed that TBX15 is one of the genes with the greatest changes at the epigenetic level in the progenitor cells of the obese, which means that it is over-expressed in these cells. “TBX15 shows a strong loss of epigenetic tags with a corresponding increase in the level of gene and protein expression,” they explain.

It was found that TBX15 is a regulator of mitochondrial mass in mast adipocytes, the main organelle in the metabolic regulation of cells responsible for cellular respiration. "The increase in TBX15 in adipose tissue in obese patients causes a change in the mitochondrial network, producing changes in shape and quantity," the researchers added.

This new study, conducted in humans, demonstrated the importance of altering epigenetic marks due to obesity in the functionality of future adipocytes, supporting the theory of progenitor dysfunction as a key event in this disease.

“We are currently studying whether this epigenetic trace is reversible, that is, if weight loss can change the epigenetic changes caused by obesity,” says Joan Vendrell.

Source: Ciber


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