Circulating lipids are linked with insulin resistance and increased cardiovascular disease risk. We previously reported that dihydroceramides, a specific type of sphingolipid, are elevated in insulin-resistant individuals; however, little is known regarding whether insulin-sensitizing lifestyle interventions can improve profiles of sphingolipids and other lipid species. A total of 21 individuals with obesity participated in a 3-month lifestyle intervention of combined weight loss and exercise training. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps, and serum lipidomics was conducted. Following the intervention, BMI was significantly reduced by 10%; VO2peak and insulin sensitivity increased by 12% and 57%, respectively; and total serum triacylglycerol (TAG), diacylglycerol, dihydroceramides, sphingosine-1-phosphate, and sphinganine-1-phosphate were significantly reduced, as were specific species of dihydroceramides (C18:0 and C24:1). Individuals with higher preintervention TAG concentrations had significant decreases in serum lipids, which were not significantly changed in individuals with lower preintervention TAG. These data show that serum sphingolipid species previously linked to insulin resistance in humans can be reduced with insulin-sensitizing lifestyle interventions. Furthermore, individuals with elevated serum TAG may significantly benefit from lifestyle interventions that increase insulin sensitivity due to a greater decrease in serum lipids related to insulin resistance.
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