Exercise-Induced N-Lactoylphenylalanine Predicts Adipose Tissue Loss during Endurance Training in Overweight and Obese Humans

Abstract

Physical exercise is a powerful measure to prevent cardiometabolic diseases. However, the individual response to lifestyle interventions is variable and cannot, to date, be predicted. N-Lactoylphenylalanine (Lac-Phe) produced during exercise has recently been shown to mediate weight loss in obese mice. Lac-Phe could also contribute to, and potentially explain differences in, the effectiveness of exercise interventions in humans. Sedentary overweight and obese subjects completed an 8-week supervised endurance exercise intervention (n = 22). Before and after the intervention, plasma levels of Lac-Phe were determined by UHPLC-MS in the resting state and immediately after an acute bout of endurance exercise. Adipose tissue volume was quantified using MRI. Acute exercise caused a pronounced increase in Lac-Phe, both before and after the intervention. Higher levels of Lac-Phe after acute exercise were associated with a greater reduction in abdominal subcutaneous and, to a lower degree, visceral adipose tissue during the intervention. Lac-Phe produced during physical activity could contribute to weight loss by acting as a signaling molecule that regulates food intake, as previously shown in mice. Quantification of Lac-Phe during an exercise test could be employed as a tool to predict and potentially improve the individual response to exercise-based lifestyle interventions in overweight humans and those with obesity.

Keywords: N-Lactoylphenylalanine (Lac-Phe); biomarker; exercise intervention; exerkine; obesity.

Figure 1

(A): Structure of N-Lactoylphenylalanine (Lac-Phe) and identification by LC-MS/MS. (B): Plasma levels of Lac-Phe in subjects with overweight and obesity (n = 22) before (resting) or immediately after (acute) a 30-min endurance exercise session before (pre) or after (post) an 8-week training intervention. (C,D): Correlation of plasma Lac-Phe with plasma phenylalanine (C) and lactate (D). (E,F): Correlation of the fold change in subcutaneous abdominal adipose tissue volume during the exercise intervention with the concentration of Lac-Phe after acute exercise before (pre-training, (E) and after the exercise intervention (post-training, (F). R², standardized beta coefficient (Beta) and p-value are shown for the simple linear regression (values from multiple regression presented in Table 2). AU, arbitrary units.