Metabolic flexibility to lipid during exercise is not associated with metabolic health outcomes in individuals without obesity

A low metabolic flexibility to lipid (MetF-lip) in skeletal muscle may promote ectopic lipid accumulation, thus inducing metabolic disturbances. We aimed to determine the association between MetF-lip in skeletal muscle and metabolic health outcomes in individuals without obesity. We also explored the association between MetF-lip and the inflammatory signaling pathway in skeletal muscle. This was a cross-sectional study in 17 individuals aged (median [IQR]) 55.4 [48.6, 58.5] years, with a BMI of 24.4 [22.6, 26.0] kg/m². MetF-lip was assessed as the increase in relative lipid oxidation during a single exercise session (~ 50% VO₂max, 2 hours), quantified as the drop in whole-body respiratory exchange ratio (ΔRER = RER at 2 hours - maximum RER attained). HOMA-IR, metabolic syndrome z-score, fat percentage, trunk-to-appendicular fat, and VO₂max were included as metabolic health outcomes. The abundance of proteins of the inflammatory pathway was analyzed in resting muscle. Acute exercise progressively increased relative lipid oxidation (ΔRER = -0.04 [-0.08, -0.02]). MetF-lip was not associated with any metabolic health outcome but correlated inversely with p-p38^{Thr180/Tyr182} in muscle. A low MetF-lip in skeletal muscle does not seem a major determinant of metabolic disturbances but associates with a partial activation of the inflammatory signaling in individuals without obesity.