European Journal of Endocrinology · Nov 26, 2025

The effects of acute and chronic exercise on lipocalin-2 in middle-aged and older adults: a randomized control trial

By Bauer C, Sim M, Smith C et al.

OBJECTIVE: Chronically elevated circulating lipocalin-2 (LCN2) levels are implicated in poor energy regulation, increased cardio-metabolic disease risk, and poor physical function. Exercise is known to improve these factors, but whether LCN2 is modifiable by exercise is not clear. We examined the effect of acute and chronic exercise on LCN2 levels and whether this relates to glucose regulation, body composition, and physical function. DESIGN AND METHODS: Thirty-three middle-aged and older adults (45-84 years, median body mass index 26.21 kg/m2) completed an acute high-intensity interval exercise session (HIIE). Participants were randomized to 4 weeks of high-intensity interval training (HIIT) or control. Lipocalin-2, insulin, glucose, and homeostatic model assessment for insulin resistance (HOMA-IR) were analysed in serum at baseline and immediately, 1 and 3 h post-HIIE, and post-4 weeks of HIIT. Urinary LCN2 was assessed pre and post 4 weeks of HIIT. RESULTS: A main effect for time for serum LCN2, insulin, glucose, and HOMA-IR was detected after acute-HIIE (P < .001). Circulating serum LCN2 levels increased significantly immediately post-HIIE compared to baseline (P < .001) and returned to levels similar to baseline by 60 and 180 min post-HIIE. Four weeks of HIIT improved VO2peak, yet had no significant effect on LCN2 levels or physical function. CONCLUSIONS: Acute-HIIE, but not 4 weeks of HIIT, transiently increased circulating LCN2 and improved insulin sensitivity in middle-aged and older adults. It remains unclear if LCN2 is modifiable by chronic exercise training longer than 4 weeks or in people with poor glycaemic control. CLINICAL TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12622000337774.

doi.org/10.1093/ejendo/lvaf251Open accessPubMed 41364683Interventions