Endotrophin may reveal metabolic risks linked to changing body fat

Researchers have identified a biological marker that rises and falls as body fat changes, offering new insight into how weight gain and weight loss may influence metabolic health.

Published in Metabolism, the study "Dynamic Regulation of Circulating Endotrophin by Changes in Fat Mass in Humans" found that circulating levels of endotrophin – a protein fragment released as fat tissue expands and remodels – consistently increased when people gained body fat and decreased when they lost body fat. The findings suggest endotrophin could serve as a valuable biomarker of metabolic health and may one day become a target for therapies aimed at reducing the health risks associated with obesity.

The study included researchers from LSU's Pennington Biomedical Research Center, Pontificia Universidad Católica de Chile, Touchstone Diabetes Center at the University of Texas Southwestern and Texas Therapeutics Institute at the University of Texas Health Science Center at Houston.

 "Our findings show that endotrophin closely reflects changes in body fat, even over relatively short periods of weight gain or weight loss," said LSU Boyd Professor Dr. Eric Ravussin of Pennington Biomedical. "This suggests endotrophin may help explain how excess body fat contributes to metabolic complications and provides a promising avenue for future research into new treatments."

The research analyzed data from two clinical studies involving 73 healthy adults. One study examined several six-month weight-loss strategies, including calorie restriction and increased physical activity, while the second evaluated the effects of eight weeks of controlled overfeeding. Through both studies, participants experienced changes ranging from an 11-kilogram loss to a 7-kilogram gain in body fat.

Researchers found a strong relationship between changes in body fat and circulating endotrophin levels. As fat mass increased, endotrophin levels increased. As participants lost body fat, endotrophin levels declined. The team also found evidence that endotrophin may partially explain the relationship between increased body fat and higher total cholesterol levels, suggesting the molecule could play a role in the development of metabolic disease.

"One of the most exciting aspects of this study is that endotrophin changes rapidly as fat mass changes. That makes it a dynamic indicator of adipose tissue remodeling rather than simply a marker of obesity. It also suggests that therapies targeting endotrophin could complement weight-loss approaches by directly addressing the harmful biological consequences of dysfunctional fat tissue," said Dr. Philipp Scherer, Director of the Touchstone Diabetes Center and senior author on the study.

The researchers conclude that endotrophin may represent both a useful biomarker for monitoring metabolic health and a promising therapeutic target. Additional studies are needed to determine whether reducing endotrophin can improve health outcomes in people with obesity or other metabolic disorders.

"Understanding the biological signals produced by fat tissue is essential to developing more precise approaches for preventing and treating obesity-related diseases," said Dr. Jennifer Rood, Interim Senior Vice Chancellor and Executive Director of Pennington Biomedical. "This study highlights the importance of collaboration in strengthening our ability to translate discoveries about metabolism into knowledge that could ultimately improve the prevention and treatment of chronic diseases."