Moderate iron deficiency and high dietary iron intake differentially alter hepatic lipid metabolism and adipose tissue lipid handling in mice.

Background: Iron (Fe) is an essential micronutrient, yet both its deficiency and overload have been associated with disruptions in lipid metabolism. This study investigated the effects of moderate iron deficiency and high dietary iron on lipid metabolic pathways in mice. Methods: Five-week male C57BL/6J mice were fed for 16 weeks on one of three diets: a basal iron-deficient diet without iron supplementation (FeD, 19.26 mg/kg Fe), and the same basal diet supplemented with either 200 mg Fe/kg (iron-adequate control, Control) or 1,200 mg Fe/kg (high-iron, FeH). Growth performance, iron status, serum lipids, tissue iron deposition, hepatic fatty acid composition, and expression of key genes and enzymes involved in lipid metabolism were analyzed. Results: The FeD group exhibited increased body weight and feed intake, and reduced systemic iron parameters. Molecular analysis revealed a distinct pattern of lipid metabolic disruption in FeD, characterized by the upregulation of certain hepatic lipogenic transcripts ( Conclusions: These findings demonstrate that moderate iron deficiency and high iron intake disrupt hepatic lipid metabolism via different pathways: FeD primarily through systemic adaptations leading to post-translational constraints on iron-dependent enzymes, whereas FeH acts through direct transcriptional activation of hepatic