(P16-002-23) A Novel Approach To Assess Metabolic Flexibility by Indirect Calorimetry and Related Circulating Metabolic Parameters in Humans

Objectives: Metabolic flexibility (MF) is the ability to efficiently use and store energy substrates, glucose and fat, matching fuel availability and demand to periodic fasting, varying meal composition, physical activity, and environmental variations. MF is negatively correlated with aging and age-related diseases.

We propose a novel approach to assess MF by indirect calorimetry examining the metabolic responses and the relationships between peak fatty acid oxidation (PFO) and the maximum oxygen consumption (VO2max) during ramp exercise tests.

Methods: 20 healthy volunteers (10 F; 10 M), aged 45-65, were stratified into two groups, high intensity (HI n=11) and low intensity (LI n=9) according to their referred physical activity intensity. Following overnight fasting, volunteers executed exercise tests on a leg cycle ergometer connected to a calorimeter to assess the gas respiratory exchange profile. After a 3 min of rest period, subjects started a continuous progressive intensity test with 5 min-steps of 20-30 Watts until volitional fatigue.

We suggest a numerically measurable new MF index (MFI), calculated by the product of PFO, normalized per kg of free fat mass, and %VO2max at PFO.

Results: We observed a two-fold difference of MFI values between the two groups (p < 0.001). HI individuals had higher circulating levels of DHA/EPA ratio (p < 0.05), a marker of peroxisomal beta-oxidation induced by peroxisome proliferator activated receptor (PPAR) alpha, and oleoylethanolamide (OEA) (p < 0.01), a PPAR alpha ligand, and lower levels of 2-arachidonoylglycerol (2-AG) (p < 0.01), an endogenous ligand of cannabinoid receptors.

MFI resulted positively correlated to DHA/EPA ratio and OEA, and negatively to 2-AG.

Conclusions: Our data suggest a modulation of the MF by the balance between PPAR alpha and endocannabinoid systems activity.

Ongoing studies are evaluating whether personalised nutritional and physical activity approach by modulating the balance of PPAR alpha/endocannabinoid system activity is able to modify MFI in order to validate it as reliable index of MF.

Funding Sources: Project “Kent’Erbas” REG. (UE) 1305/2013 PSR 2014-2020-19/19.2