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  2. Iron increases lipid deposition via oxidative stress-mediated mitochondrial dysfunction and the HIF1α-PPARγ pathway

Iron increases lipid deposition via oxidative stress-mediated mitochondrial dysfunction and the HIF1α-PPARγ pathway

  • Cell Mol Life Sci. 2022 Jul 4;79(7):394. doi: 10.1007/s00018-022-04423-x.
Chang-Chun Song 1 Kostas Pantopoulos 2 Guang-Hui Chen 1 Chong-Chao Zhong 1 Tao Zhao 1 Dian-Guang Zhang 1 Zhi Luo 3 4
Affiliations

Affiliations

  • 1 Laboratory of Molecular Nutrition for Aquatic Economic Animals, Fishery College, Huazhong Agricultural University, Wuhan, 430070, China.
  • 2 Lady Davis Institute for Medical Research and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.
  • 3 Laboratory of Molecular Nutrition for Aquatic Economic Animals, Fishery College, Huazhong Agricultural University, Wuhan, 430070, China. luozhi99@mail.hzau.edu.cn.
  • 4 Hubei Hongshan Laboratory, Fishery College, Huazhong Agriculture University, Wuhan, 430070, China. luozhi99@mail.hzau.edu.cn.
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.

Keywords

Iron overload; Lipid metabolism; Mitochondrial dysfunction; Oxidative stress.

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