Why Does Belly Fat Turn into a “Callus”? ... With Visceral Fat, Its Condition Matters More Than “How Much” [Health Talk]

[Financial News] At the same weight, some people develop diabetes while others remain perfectly healthy. The difference may lie in the “quality” of the visceral fat inside the abdomen.
South Korean researchers have identified THBS1 (thrombospondin-1), a key protein that hardens visceral fat and causes inflammation. They also confirmed that inhibiting THBS1 reduces fibrosis and inflammation in adipose tissue, suggesting it could become a new diagnostic marker and therapeutic target for metabolic diseases.
A joint research team comprising Choi Seong-hui and Moon Jun-ho, professors in the Division of Endocrinology and Metabolism at Seoul National University Bundang Hospital, and Kim Jong-kyung, a professor in the Department of Life Sciences at Pohang University of Science and Technology (POSTECH), along with first authors Dr. Jeong Ji-su and Dr. Park Eun-seo, said it had identified THBS1, a protein that causes inflammation and fibrosis in adipose tissue as obesity and diabetes progress. The team conducted a detailed, cell-level analysis of visceral fat from Koreans. The findings were published online in the international journal Nature Communications on the 27th of last month.
Adipose tissue is both a storehouse for excess energy and an organ that regulates inflammation throughout the body. Visceral fat, which accumulates between abdominal organs, is more prone than subcutaneous fat to inflammation and fibrosis (the process by which tissue hardens like scar tissue) and is more closely associated with insulin resistance, type 2 diabetes and cardiovascular disease.
However, adipose tissue contains a mixture of fat cells, adipose stem cells, immune cells and vascular cells, so it was unclear which cells changed, and how, to make fat “unhealthy.” Earlier studies grouped together people with varying degrees of obesity, making it difficult to identify differences between disease stages.

The research team compared visceral fat from 21 Koreans who underwent surgery at Seoul National University Bundang Hospital, dividing them into three groups: normal-weight (8), obese (5), and obese with diabetes (8). The normal-weight group consisted of kidney donors, while the other 13 were patients who underwent sleeve gastrectomy (a metabolic and bariatric surgery).
Using “single-cell nuclear RNA analysis,” a technique that reads which genes are active in each individual cell, the team analyzed about 86,000 cells and created a “cell map” of visceral fat.
The team found distinct populations of adipose stem cells and fat cells that produced large amounts of THBS1. These cells had significantly higher expression of genes associated with fibrosis and inflammation, and were more abundant in the obese group than in the normal-weight group, and in the obese-with-diabetes group than in the obese group.
The amount of THBS1 in fat cells also rose in order from the normal-weight group to the obese group and then the obese-with-diabetes group. Higher body mass index (BMI) and glycated hemoglobin (HbA1c, an indicator of average blood glucose over the past 2–3 months) were associated with higher levels of THBS1. Inflammation-causing immune cells (SLC11A1-positive macrophages) were also much more numerous in the obese-with-diabetes group.

The team investigated how THBS1 works through cell experiments, experiments using cultured adipose tissue from humans and mice, and animal studies. THBS1 stimulated macrophages in adipose tissue and activated TGF-β, a signaling molecule involved in fibrosis. As a result, collagen accumulated in the adipose tissue and inflammation increased.
THBS1 also interfered with the process by which adipose stem cells develop into healthy fat cells. It also reduced glucose uptake and insulin signaling in mature fat cells. When the team increased THBS1 in the visceral fat of mice, collagen accumulated and inflammatory immune cells flocked to the tissue. This means THBS1 turns healthy fat, which stores energy effectively, into hard, inflamed tissue. The researchers also found that YAP/TAZ signaling, which is activated when cells are under stress, such as when fat cells enlarge, is an upstream regulator that directly switches on the THBS1 gene.
When an antibody that blocks THBS1 was applied to visceral adipose tissue from patients with obesity and diabetes, expression of genes associated with fibrosis and inflammation fell. In an experiment in which the antibody was administered to mice made obese by a high-fat diet, fibrosis in adipose tissue also decreased significantly.
The team said THBS1 may also be used as a biomarker to assess the health of adipose tissue through a blood test. However, it added that further validation in larger and more diverse groups will be needed before the marker can be used for diagnosis.
The team said this was the first report to systematically document changes in adipose tissue as metabolic diseases progress by analyzing visceral fat at the cellular level in a Korean cohort with clearly defined disease stages, and to identify THBS1 as a key factor and verify its function. The study is seen as offering a clue toward treatment strategies that improve not only the “quantity” of fat but also its “quality,” unlike current obesity treatments, which focus on weight loss.
Professor Choi Seong-hui said, “Even at the same body weight, the risk of metabolic diseases such as diabetes may vary depending on how healthy a person’s visceral fat is.” She added, “It is significant that we directly confirmed a key factor that makes adipose tissue diseased in tissue from Korean patients. We will continue follow-up research so this can lead to the development of diagnostic and therapeutic technologies targeting THBS1.”
The study was supported by the Korea Health Industry Development Institute and the National Research Foundation of Korea (NRF), and the team filed a domestic patent application for the related technology.
 

[email protected] Jeong Myeong-jin, Medical Correspondent Reporter