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-p38Thr180/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.