Unsaturated fatty acids enhance metabolic flexibility by accelerating time-based RQ dynamics.

BACKGROUND: The quality of dietary fatty acids may influence metabolic flexibility and metabolic health. OBJECTIVES: To determine whether dietary fatty acid quality, independent of total fat content, differentially affects postprandial metabolic flexibility assessed using time-based respiratory quotient (RQ) dynamics and acylcarnitine profiles. METHODS: Fourteen healthy young men completed three randomized, single-blind crossover trials with isoenergetic high-fat meals enriched in palmitic acid (PA), oleic acid (OA), or α-linolenic acid (ALA), each providing 45% of total energy from fat. Whole-body energy metabolism was assessed using indirect calorimetry over 13 hours, and blood and urine samples were collected for acylcarnitine analysis. RESULTS: Time to peak RQ was shorter in the OA trial than in the PA trial (68 ± 53 vs. 166 ± 101 min; P = 0.023). Time to food quotient (FQ) was shorter in both the OA and ALA trials than in the PA trial (239 ± 40 and 237 ± 86 vs. 271 ± 27 min; P = 0.030 and 0.007, respectively). The serum C2-acylcarnitine-to-free carnitine ratio was higher in the OA trial than in the PA trial in both postprandial (P = 0.004) and next-morning fasting states (P = 0.009). Urinary C2-acylcarnitine concentrations were higher in the OA (P = 0.006) and ALA (P = 0.041) trials than in the PA trial. Serum and urinary acylcarnitine indices were significantly associated with time to FQ but not with time to peak RQ. CONCLUSIONS: Despite being isoenergetic and containing the same proportion of energy from fat, meals enriched in unsaturated fatty acids promoted faster time-based RQ dynamics and more efficient postprandial substrate switching than PA-rich meals, accompanied by distinct acylcarnitine responses. These findings suggest that dietary fatty acid quality influences metabolic flexibility and support the integration of time-based RQ dynamics and acylcarnitine profiling to characterize its functional and metabolic components. CLINICAL TRIAL REGISTRY: This trial was registered at https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000057763 as UMIN000050707.