The Effect of Endurance Training and Chlorogenic Acid Supplementation on Hepatic Gluconeogenesis Pathway in Obese Pre-Diabetic Mice

Document Type : Research Paper I Open Access I Released under (CC BY-NC 4.0) license

Authors

1 Researcher in Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Isfahan, Isfahan, Iran.

2 Professor of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Isfahan, Isfahan, Iran.

3 Assistant Professor of Embryology, Royan Isfahan Biotechnology Research Institute, Isfahan, Iran.

4 Professor of Embryology, Royan Isfahan Biotechnology Research Institute, Isfahan, Iran.

Abstract

Background & purpose: Hepatic gluconeogenesis and insulin resistance are key features of the prediabetic state. Chlorogenic acid, a polyphenolic compound with anti-diabetic properties, and endurance exercise, as a non-pharmacological intervention, both play important roles in improving glucose metabolism. This study aimed to investigate the effects of endurance training and chlorogenic acid supplementation on hepatic gluconeogenic pathway in obese prediabetic mice. Methods: Obese male prediabetic rats were divided into four groups: prediabetic control (PreD), endurance exercise (PreD/Ex), chlorogenic acid (PreD/AC), and the combination of both interventions (PreD/AC.Ex). After the intervention period, fasting blood glucose (FBS), plasma insulin, and glucose tolerance test (GTT) were measured. The hepatic expression of key gluconeogenic genes, PCK and G6PC2, was analyzed using RT-qPCR. Results: Both endurance exercise and chlorogenic acid significantly reduced fasting blood glucose and plasma insulin levels compared with the prediabetic group (p<0.001). Glucose tolerance was markedly improved in all intervention groups. Moreover, endurance training significantly increased hepatic expression of PCK and G6PC2, while chlorogenic acid supplementation, particularly when combined with exercise, suppressed this increase (p<0.05). Conclusion: The combined effect of endurance exercise and chlorogenic acid improves glucose homeostasis and attenuates hepatic gluconeogenic gene expression, suggesting a synergistic potential in modulating liver metabolism and preventing the progression from prediabetes to type 2 diabetes.

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Articles in Press, Accepted Manuscript
Available Online from 26 February 2026
  • Receive Date: 08 November 2025
  • Revise Date: 06 January 2026
  • Accept Date: 26 February 2026