Why obesity alters the function of adipocytes – Digital AIM


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

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

Although traditionally considered due to an imbalance between intake and energy expenditure that favored fat storage, it is now recognized that interactions between environmental and genetic factors (what is known as epigenetics) play a key role in its development. .

Researchers from the Center for Biomedical Research in the Diabetes and Metabolic Diseases Associated Network (Ciberdem), from the group led by Joan Vendrell and Sonia Fernández-Veledo at the Pere Virgili Sanitary Research Institute (IISPV) (Catalunya, Spain), have just given one more step in the knowledge of the processes that trigger these gene-environment interactions.

Experts have identified a new mechanism by which obesity leaves an epigenetic mark on the adipocyte precursor cells that determines the malfunction of the new fat cells that are generated.

Previous studies of the same group have previously revealed that adipocyte precursor cells in obese patients do not function properly. However, to date, the molecular basis of these changes was unknown.

"Subcutaneous adipose tissue from obese individuals contains a dysfunctional set of adipocyte precursor stem cells and there is evidence of an association between obesity and loss of function of these stem cells," explains Sonia Fernández Veledo, the last signer of the study that closes for be published in the International Journal of Obesity.

An adequate functional population of adipocyte precursors is crucial in the proper expansion of adipose tissue, in lipid management and in the prevention of lipotoxicity against positive and chronic energy balance (ie when all calories ingested are not "burned"). .

"We believe that a better understanding of the biology of this set of precursor stem cells could contribute to the development of new strategies to fight obesity or promote the expansion of healthy adipose tissue," he adds.

To this end, stem cells derived from adipose tissue (precursors) and mature adipocytes from healthy, lean and obese patients were studied.

"Our work shows that obesity induces important epigenetic changes in the DNA of precursor cells, which determines the malfunction of new adipocytes that are generated," says Joan Vendrell, leader of the Cyberdem group at IISPV.

"Obesity conditions adipocyte precursor stem cells with a dynamic loss of DNA methylation in selected regions that may cause white adipose tissue dysfunction and the development of metabolic syndromes in obesity," he explains.

One of the most modified genes is the transcription factor TBX15, a factor involved in adipogenesis, fat distribution and "darkening" (the transformation of white fat into brown fat, which is healthy and necessary for 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 that it is overexpressed in these cells. "TBX15 shows a strong loss of epigenetic marks with a corresponding increase in the level of gene and protein expression," they explain.

The study identified that TBX15 is a regulator of the mitochondrial mass in obese adipocytes, a basic organelle in the metabolic regulation of cells responsible for cellular respiration. "The increase of TBX15 in the adipose tissue of obese patients causes a change in the mitochondrial network, producing changes in form and number," added the researchers.

This new research in humans has demonstrated the importance of altering epigenetic marks 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 studying whether this epigenetic footprint is reversible, that is, whether weight loss can reverse obesity-induced epigenetic changes," says Joan Vendrell.

Source: Ciber


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