Gender-based heterogeneity of FAHFAs in trained runners

Fatty acid esters of hydroxy fatty acid (FAHFA) are anti-diabetic and anti-inflammatory lipokines. Recently FAHFAs were also found to predict cardiorespiratory fitness in trained runners. Here we compared the association between circulating FAHFA baseline concentrations and body composition, determined by dual x-ray absorptiometry, in female runners who were lean (BMI < 25 kg/m², n = 6), to those who were overweight (BMI ≥ 25 kg/m², n = 7). We also compared circulating FAHFAs in lean male runners (n = 8) to the same trained lean female (n = 6) runner group. Circulating FAHFAs were increased in females in a manner that was modulated by specific adipose depot sizes, blood glucose, and lean body mass. As expected, circulating FAHFAs were diminished in the overweight group, but, strikingly, in both lean and overweight cohorts, increases in circulating FAHFAs were promoted by increased fat mass, relative to lean mass. These studies suggest multimodal regulation of circulating FAHFAs and raise hypotheses to test endogenous FAHFA dynamic sources and sinks in health and disease, which will be essential for therapeutic target development. Baseline circulating FAHFA concentrations could signal sub-clinical metabolic dysfunction in metabolically healthy obesity.