THE ACUTE METABOLOMIC EFFECTS OF A FATMAX TEST IN PEOPLE WITH GILBERT’S SYNDROME AND IN HEALTHY CONTROLS

Author(s): STELZER, T., SPAHITS, H., KRIPP, A.M., DRAXLER, A., MAQBOUL, L., KÖNIG, D., WAGNER, K.H., Institution: UNIVERSTIY OF VIENNA, Country: AUSTRIA, Abstract-ID: 887

INTRODUCTION:
Greater levels of ketone bodies have been found in Gilbert’s syndrome (GS), a mild hyperbilirubinemic condition, compared to healthy controls (Hana et al., 2021). These findings indicate that GS may lead to a higher fat oxidation, which might explain the better lipid profile and lower BMI in people with GS, which was found in several previous studies. To analyze maximal fat oxidation (MFO), and therefore their fat oxidation capacity, we conducted a FatMax test. In this test, participants are supposed to oxidate a maximum amount of fat, which may lead to shifts in their metabolome and highlights the importance of this test in GS.
METHODS:
In a human case control study, where controls were age and gender matched, 40 GS subjects (UCB>17μmol/l) and 40 controls (C) between 18 and 65 years of age were included. All participants were healthy, moderately physically active and nonsmokers. After having fasted for 12 h overnight, all subjects completed a graded exercise test on a cycle ergometer, which was terminated at RER=1.00. Before and after the test venous blood samples were taken. To analyze potential shifts in the plasma metabolome, we employed an untargeted metabolomics approach using liquid chromatography/mass spectrometry (LC/MS).
RESULTS:
No differences between GS and C group were found at baseline or after the FatMax test in the metabolome. However, the graded test resulted in significant changes of 227 metabolite levels when analyzing the complete study population. The results predominantly showed changes in lipid metabolism. More specifically, an increase in several fatty acid (FA) families, predominantly unsaturated fatty acids, was observed. Furthermore, a significant pathway hit was found for “biosynthesis of unsaturated FA” and “purine metabolism”. Interestingly, this slight trend to greater metabolome shift and increase in FA, was observed in participants with a higher maximal fat oxidation and FatMax.
CONCLUSION:
Even though, we could not replicate earlier findings regarding the lipid profile of GS participants, we made some interesting findings concerning the FatMax test. As FA increased post exercise, it can be concluded that mobilization during the test was higher than oxidation. Moreover, the metabolome could also be considered as a tool to identify (high) fat oxidation.