Effects of moderate- and high-intensity aerobic exercise on hepatic iron homeostasis, ferroptosis-related changes, and lipid metabolism in high-fat diet-induced MASLD rats.

Authors

Shijie Wang, Chang Li, Yufei Liu, Lin Xu

Published in

Biochemical and biophysical research communications. Volume 834. Pages 154467. Aug 20, 2026. Epub Aug 20, 2026.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with disrupted iron homeostasis, lipid peroxidation, and ferroptosis-related liver injury. Although exercise is recommended for MASLD management, whether moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) exert comparable effects on hepatic iron metabolism and ferroptosis-related changes remains unclear. This study compared the effects of MICT and HIIT on hepatic iron homeostasis, ferroptosis-related markers, and lipid metabolic remodeling in high-fat diet (HFD)-induced MASLD rats. Forty male Sprague-Dawley rats were assigned to a normal-fat diet group or an HFD group. After 8 weeks of HFD feeding, HFD-fed rats were further divided into HFD control, MICT, and HIIT groups and underwent an additional 8-week intervention. HFD feeding induced metabolic dysfunction, hepatic steatosis, liver injury, iron accumulation, increased activation-related markers of the IL-6/JAK2/STAT3-hepcidin pathway, and ferroptosis-related changes, including reduced GPX4 and increased PTGS2 and MDA. Both MICT and HIIT improved metabolic and histological outcomes, reduced hepatic Fe²⁺ accumulation and lipid peroxidation, increased FPN1 expression, decreased DMT1 expression, reduced activation-related markers of IL-6/JAK2/STAT3-hepcidin signaling, and improved antioxidant defense. Untargeted lipidomics indicated partial remodeling of HFD-induced disturbances in glycerophospholipid, glycerolipid, sphingolipid, ether lipid, thermogenesis, insulin-resistance, and AMPK-related pathways. Most endpoint outcomes did not differ significantly between MICT and HIIT. Because no pathway-specific manipulation, iron-rescue experiment, or ferroptosis inhibitor was used, the present data do not establish that the IL-6/JAK2/STAT3-hepcidin-FPN1 axis causally mediates the exercise response. Instead, the findings indicate that MICT and HIIT exert broadly comparable protective effects that are associated with improved hepatic iron homeostasis, lower ferroptosis-related susceptibility, and hepatic lipid metabolic remodeling.

PMID:
42632327
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

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