The effect of prednisolone ingestion and acute exercise on lipocalin-2 and its variants in young men: a pilot randomised crossover study

Lipocalin-2 (LCN2) has three main variants; polyaminated (hLCN2) and non-polyaminated (C87A and R81E). The polyaminated form is proposed to positively influence energy control, whereas the non-polyaminated forms negatively impact energy control in mice. Glucocorticoids negatively affect glucose regulation and exercise has a positive effect. We hypothesise that glucocorticoids will suppress, while exercise will increase hLCN2, and decrease C87A and R81E, which will be associated with improved insulin sensitivity. In a randomised crossover design, nine young healthy men (aged 27.8 ± 4.9 years; BMI 24.4 ± 2.4 kg/m²) completed 30 min of high-intensity aerobic exercise (90-95% heart rate reserve) after glucocorticoid or placebo ingestion. Blood was collected and analyzed for LCN2 and its variants levels at baseline, immediately, 60 min and 180 min post-exercise. Insulin sensitivity was assessed using hyperinsulinemic-euglycemic clamp. A main effect, increase in LCN2 was detected for prednisolone ingestion (overall treatment effect p = 0.001), but not LCN2 variants (all p > 0.05). Main effects for time were observed for exercise for LCN2 and all variants (overall time effect all p < 0.02). Regardless of treatment, LCN2, C87A, R81E, and hLCN2 increased immediately after exercise compared with baseline (all p < 0.04). C87A, but not LCN2 or its other variants, remained elevated at 180 min post-ex (p = 0.007). LCN2, but not its variants, was elevated in response to prednisolone ingestion. LCN2 and its variants are transiently increased by acute exercise, but this increase was not related to insulin sensitivity. The clinical implication of elevated LCN2 and its variants post-exercise on satiety and energy regulation, as well as the mechanisms involved warrant further investigation.Clinical trial registration: www.anzctr.org.au , ACTRN12615000755538.