UNIST Identifies Correlation Between Endotrophin Accumulation in Adipocytes and Diabetes

Recent research on the relationship between obesity and diabetes has attracted attention.

The team led by Professor Ji-Young Park from the Department of Life Sciences at Ulsan National Institute of Science and Technology (UNIST) conducted an analysis of the endotrophin protein, which provides the environment necessary for cell growth and differentiation.

As a result of the analysis, the research team revealed for the first time in the world that endotrophin protein, which increases in an obese state, enters fat cells and controls autophagy that destroys unnecessary cells, thereby causing inflammation and diabetes.

This study is expected to be utilized in research on the treatment of metabolic diseases and cancer related to obesity caused by inflammation and autophagy abnormalities.

Endotrophin is an extracellular matrix protein that responds to metabolic stress outside the cell in the case of obesity, first discovered by Professor Ji-Young Park in 2012.

Ulsan National Institute of Science and Technology (UNIST) is home to Professor Ji-Young Park of the Department of Life Sciences.

In an obese state, endotrophin levels increase, which is known to worsen diabetes by increasing fibrosis, inflammation, and insulin resistance in adipose tissue.

The research team conducted a comparative analysis between obese and non-obese states to closely examine the pathway through which endotrophin moves inside and outside the cell. In the obese state, endotrophin accumulates in fat cells through endocytosis, a process by which extracellular substances move into the cell.

It was newly revealed that this not only promotes the formation of autophagosomes involved in autophagy but also inhibits the degradation of autophagosomes, causing abnormalities in autophagy that lead to cell death, inflammation, and insulin resistance.

Specifically, endotrophin entering fat cells promotes the formation of autophagosomes mediated by SEC13, a protein related to protein transport, and ATG7, a protein important for autophagosome formation.

Additionally, autophagosomes accumulated by endotrophin disrupt the balance of the autophagy process, causing fat cell death, increased inflammation, and worsening insulin resistance.

At this time, it was also confirmed that inhibiting the function of the ATG7 protein using the siRNA system, which interferes with specific gene expression, or neutralizing endotrophin improves obesity-related metabolic diseases.

Professor Ji-Young Park of the Department of Life Sciences explained, “The accumulation of endotrophin inside cells can be used as a biomarker indicating an imbalance in extracellular matrix homeostasis,” adding, “Efficient removal of excessively produced endotrophin in obese adipose tissue could be a promising therapeutic strategy for treating obesity and obesity-related metabolic diseases.”

The results of this study were pre-published online on June 10 in the international journal in the field of endocrine metabolism, Metabolism: Clinical and Experimental, and are scheduled for formal publication.

This research was conducted with the support of the Ministry of Science and ICT and the National Research Foundation of Korea (Bio·Medical Technology Development Project, Individual Basic Mid-Career Research Project, Leading Research Center).

This content was produced with the assistance of AI translation services.