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

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 significan...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2022-07, Vol.79 (7), p.394-394, Article 394
Main Authors: Song, Chang-Chun, Pantopoulos, Kostas, Chen, Guang-Hui, Zhong, Chong-Chao, Zhao, Tao, Zhang, Dian-Guang, Luo, Zhi
Format: Article
Language:English
Subjects:
Accumulation
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Catfish
Cell Biology
Dehydrogenases
Deposition
Enzymes
Fatty acids
Fisheries
Gene expression
Homeostasis
Hydroxylase
Hypoxia
Hypoxia-inducible factor 1
Hypoxia-inducible factors
Intestine
Iron
Kinases
Laboratories
Life Sciences
Lipids
Lipogenesis
Lipolysis
Metabolism
Metabolites
Mitochondria
Nutrition research
Original
Original Article
Oxidative Stress
Peroxisome proliferator-activated receptors
Physiology
PPAR gamma - genetics
Prolyl hydroxylase
Proteins
Trace elements
Vertebrates
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Summary: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 fpn 1). 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.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-022-04423-x