TOPLINE

Endotrophin, a protein fragment released when fat tissue remodels, increased when people gained body fat and decreased when they lost body fat, researchers found.

METHODOLOGY

• To assess the relationship between short-term changes in fat mass and circulating endotrophin levels, researchers pooled individual participant data from two Pennington Biomedical trials, CALERIE 1 and EAT, including a total of 73 healthy adults. 
• Forty-two CALERIE 1 participants were randomly assigned to 6 months of weight maintenance, calorie restriction, calorie restriction with exercise, or a very low-calorie diet. 
• Thirty-one EAT participants underwent 8 weeks of 40% overfeeding. 
• Fat mass was measured by DEXA; circulating endotrophin was measured by immunoassay before and after the interventions. 

TAKEAWAY

• Changes in fat mass ranged from an 11-kg loss to a 7.0-kg gain overall. 
• These changes were positively associated with changes in circulating endotrophin in both directions of weight change. 
• The associations held after adjusting for sex, age, baseline values, and study cohort. 
• Endotrophin was estimated to mediate about 15% of the effect of change in fat mass percentage on total cholesterol; no mediation was seen for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides. 

IN PRACTICE

“Changes in circulating endotrophin concentrations reflect ongoing changes in fat mass and potentially mediate part of the effect of fat on cardiovascular health markers in humans,” the authors of the study wrote. “Targeting endotrophin may help mitigate some of the adverse effects of the progressive weight gain that occurs during adulthood….”

SOURCE

Rodrigo Fernandez-Verdejo, PhD, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, led the study, which was published online in Metabolism.

LIMITATIONS

The study had several limitations. The researchers could not establish causality between changes in fat mass and endotrophin, or between endotrophin and cholesterol changes. Mediation analyses were exploratory, based on a modest sample size, and produced wide CIs. The two pooled trials differed in interventions, sex distribution, and endotrophin assay conditions.

DISCLOSURES

The study was partially supported by grants from the UT Southwestern Medical Center and Pennington Biomedical Research Center, Cancer Prevention and Research Institute of Texas, and The Welch Foundation to one of the authors. Three authors were named as inventors on patent applications filed by The University of Texas System covering anti-endotrophin antibodies; two of those authors were also scientific cofounders of PriveBio.