The Hepatokine Leukocyte Cell-Derived Chemotaxin-2 Is Elevated in People with Impaired Glycaemic Regulation and Augmented by Acute Exercise

Engin, Buket; Willis, Scott A.; Malaikah, Sundus; Sargeant, Jack A.; Stensel, David J.; Jelleyman, Charlotte; Ennequin, Gaël; Aithal, Guruprasad P.; Yates, Thomas; King, James A.

Abstract

The hepatokine leukocyte cell-derived chemotaxin-2 (LECT2) promotes insulin resistance and hepatic fibrogenesis. In rodents, acute exercise suppresses circulating LECT2; however, human data are lacking. This study compared circulating LECT2 across populations and explored whether acute exercise impacts circulating LECT2. In Part A (n = 43), data were pooled from three experimental studies, regarding the following groups: healthy individuals, individuals with impaired glycaemic regulation (IGR), and individuals with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (T2DM-MASLD). Generalised linear models assessed differences in circulating LECT2 among groups. Part B (n = 20) involved exercise (30 min, 65% peak oxygen uptake) and control (resting) trials in the healthy and IGR groups. Circulating LECT2 was measured before and at 0, 1, 2 and 3 h post-exercise. Generalised estimating equations assessed differences in LECT2 responses to the trials among groups. In Part A, circulating LECT2 levels were 28.7% and 37.3% higher in the IGR and T2DM-MASLD groups, vs. healthy individuals (p ≤ 0.038), with BMI identified as the main predictor (p = 0.008). In Part B, average circulating LECT2 levels were 6.3% higher after exercise vs. in the control (p < 0.001), with similar responses between groups (p = 0.829). In the combined cohort, circulating LECT2 levels were elevated 1–3 h after exercise vs. control (p ≤ 0.009). LECT2 is elevated in people with dysglycaemia, with BMI as a leading predictor. Contrary to previous rodent work, acute exercise augments, rather than suppresses, circulating LECT2 in humans.

Citation

Engin, B., Willis, S. A., Malaikah, S., Sargeant, J. A., Stensel, D. J., Jelleyman, C., …King, J. A. (2024). The Hepatokine Leukocyte Cell-Derived Chemotaxin-2 Is Elevated in People with Impaired Glycaemic Regulation and Augmented by Acute Exercise. Livers, 4(1), 51-62. https://doi.org/10.3390/livers4010005

• Journal Article Type: Article
• Acceptance Date: Dec 25, 2023
• Online Publication Date: Jan 17, 2024
• Publication Date: 2024-03
• Deposit Date: Jan 23, 2024
• Publicly Available Date: Jan 25, 2024
• Journal: Livers
• Print ISSN: 2673-4389
• Electronic ISSN: 2673-4389
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 1
• Pages: 51-62
• DOI: https://doi.org/10.3390/livers4010005
• Keywords: Hepatokines; physical activity; insulin sensitivity; diabetes; leukocyte cell-derived chemotaxin 2
• Public URL: https://nottingham-repository.worktribe.com/output/29842141
• Publisher URL: https://www.mdpi.com/2673-4389/4/1/5