Iron Increases Lipid Deposition Via Oxidative Stress-mediated Mitochondrial Dysfunction and the HIF1α-PPARγ Pathway

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2022 Jul 5

PMID 35786773

Authors

Chang-Chun Song

Kostas Pantopoulos

Guang-Hui Chen

Chong-Chao Zhong

Tao Zhao

Dian-Guang Zhang

Zhi Luo

Affiliations

Soon will be listed here.

Abstract

Iron is an essential micro-element, involved in multiple biological activities in vertebrates. Excess iron accumulation has been identified as an important mediator of lipid deposition. However, the underlying mechanisms remain unknown. In the present study, we found that a high-iron diet significantly increased intestinal iron content and upregulated the mRNA expression of two iron transporters (zip14 and fpn1). Intestinal iron overload increased lipogenesis, reduced lipolysis and promoted oxidative stress and mitochondrial dysfunction. Iron-induced lipid accumulation was mediated by hypoxia-inducible factor-1 α (HIF1α), which was induced in response to mitochondrial oxidative stress following inhibition of prolyl hydroxylase 2 (PHD2). Mechanistically, iron promoted lipid deposition by enhancing the DNA binding capacity of HIF1α to the pparγ and fas promoters. Our results provide experimental evidence that oxidative stress, mitochondrial dysfunction and the HIF1α-PPARγ pathway are critical mediators of iron-induced lipid deposition.

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