Korean Researchers Identify FSTL1, a Fat-Secreted Protein, as a Potential Obesity Treatment Target

Korean researchers have found that FSTL1, a protein secreted by fat cells, may improve obesity and metabolic disease by acting through nerves to make white fat more like brown fat.

Professor Gao Yan’s team at the Institute of Basic Medical Sciences at 수도의과대학 announced the findings in the international journal Advanced Science on the 8th.

Browning of white fat increases energy expenditure and is a promising strategy for preventing obesity and metabolic syndrome. Fat tissue is innervated by the sympathetic nervous system, and fat cells also secrete various factors that regulate nerve density, creating a two-way interaction.

The team focused on the marked increase in expression of follistatin-like protein 1 (FSTL1) during the browning of white fat. However, it was not known whether FSTL1 acts directly on fat cells or through other nearby cells.

Experiments showed that FSTL1 did not directly induce browning in fat cells. Instead, it bound to TrkB receptors on the surface of sympathetic neurons and entered the neurons, then induced browning of white fat by increasing sympathetic nerve distribution in fat tissue.

When the team overexpressed FSTL1 in the fat tissue of mice, body temperature and resistance to cold increased, as did energy expenditure. In mice made obese by a high-fat diet, weight gain was suppressed, blood glucose regulation and insulin sensitivity improved, and blood cholesterol and triglyceride levels decreased.

Conversely, mice lacking FSTL1 had reduced heat production in response to cold and more severe obesity and metabolic abnormalities on a high-fat diet. Chemically removing sympathetic nerves eliminated FSTL1’s browning effect, confirming that the protein’s action depends entirely on nerves.

“We were the first to establish that FSTL1 acts as a fat cell-derived neurotrophic factor and mediates interactions between fat and the sympathetic nervous system,” the team said. “It could be a new therapeutic target for obesity and metabolic disease.”

The team added that because the study used cell lines, further validation in primary sympathetic neurons is needed, and the possibility of FSTL1 toxicity in multiple organs remains.