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Saturated fatty acid consumption is linked to the development of obesity and diabetes, however; little is understood about the influence of SFA consumption on skeletal muscle on substrate selection.Considering that metabolic inflexibility is a hallmark of the metabolic syndrome, our goal was to assess the influence of five days of high SFA feeding on skeletal muscle substrate selection from the fasted to fed state, in healthy, non-obese humans.Acute SFA feeding suppressed fasting glucose oxidation by 50%.One of the most striking findings of the study was that the high SFA diet also disrupted transcriptional regulation of lipid oxidation.