Caught the "Endotrophin" That Causes Obesity... UNIST Finds Clues to Improving Metabolic Diseases with Natural Compounds [Reading Science]

Blocking Endotrophin Production with Nigericin
Simultaneous Improvement of Inflammation and Insulin Resistance

A technology has been proposed to block "endotrophin," a key substance that worsens obesity and diabetes, using a natural compound. Experts say this opens up the possibility of a new therapeutic strategy that directly targets the causes of metabolic diseases.

On March 24, Professor Park Jiyoung’s research team from the Department of Biological Sciences at Ulsan National Institute of Science and Technology (UNIST) announced that the natural compound "nigericin" suppresses the production of endotrophin generated in obese adipose tissue, thereby improving fibrosis, inflammation, and insulin resistance simultaneously.

The process by which nigericin prevents the cleavage of collagen and suppresses the production of endotrophin. Nigericin binds to type VI collagen and inhibits cleavage by matrix metalloproteinases (MMPs), thereby suppressing the production of endotrophin. This process has been shown in animal experiments to reduce fibrosis and inflammation in adipose tissue, as well as to improve insulin resistance. Courtesy of the research team

Endotrophin is a signaling protein produced when collagen around adipocytes is cleaved. It is known to be excessively increased in obese states, impairing adipose tissue function and exacerbating metabolic diseases such as diabetes.

The research team identified that nigericin binds directly to the precursor of endotrophin, collagen (COL6A3), thereby blocking access by enzymes that cleave collagen and suppressing the production of endotrophin itself. Unlike existing treatments, which indirectly regulate inflammation or gene expression, this approach blocks the "starting point" of pathological signaling.

"Blood Sugar Down by 30% in Animal Studies... Metabolic Function Improved"

The effect was also confirmed in animal experiments. When nigericin was administered to mice made obese through a high-fat diet, fibrosis and inflammatory responses in adipose tissue decreased, fasting blood glucose dropped by approximately 30%, and insulin sensitivity improved. No abnormalities in liver or kidney function were observed.

The research team screened over 1,000 natural compounds in stages and identified nigericin as a substance capable of reliably suppressing endotrophin production even in hypoxic conditions. Nigericin is a natural compound produced by actinomycetes.

Professor Park Jiyoung stated, "It is meaningful in that we have presented a new molecular mechanism that directly blocks the process of endotrophin production," adding, "There is potential to expand this to a variety of metabolic diseases accompanied by adipose tissue fibrosis, not just obesity and diabetes."

This research was supported by the Ministry of Science and ICT and the National Research Foundation of Korea, and was published online in the international journal "Experimental & Molecular Medicine" on March 5.

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