title: Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans.
abstract: The trace element iron is crucial for living organisms, since it plays essential roles in numerous cellular functions. Systemic iron overload and the elevated level of ferritin, a ubiquitous intracellular protein that stores and releases iron to maintain the iron homeostasis in cells, has long been epidemiologically associated with obesity and obesity-related diseases. However, the underlying mechanisms of this association remain unclear. Here, using Caenorhabditis elegans, we show that iron overload induces the expression of sgk-1, encoding the serum and glucocorticoid-inducible kinase, to promote the level of ferritin and fat accumulation. Mutation of cyp-23A1, encoding a homolog of human cytochrome P450 CYP7B1 that is related to neonatal hemochromatosis, further enhances the elevated expression of ftn-1, sgk-1, and fat accumulation. sgk-1 positively regulates the expression of acs-20 and vit-2, genes encoding homologs of the mammalian FATP1/4 fatty acid transport proteins and yolk lipoproteins, respectively, to facilitate lipid uptake and translocation for storage under iron overload. This study reveals a completely novel pathway in which sgk-1 plays a central role to synergistically regulate iron and lipid homeostasis, offering not only experimental evidence supporting a previously unverified link between iron and obesity, but also novel insights into the pathogenesis of iron and obesity-related human metabolic diseases.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Haizhen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Xue
authors.identifier: 0000-0001-9131-5478
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Jieyu
authors.initials: J
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Linqiang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Jingfei
authors.initials: J
authors.lastname: Huang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Yuru
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Life Science and Biotechnology, Key Laboratory of Special Biological Resource Development and Utilization of University in Yunnan Province, Kunming University, Kunming 650214, China xiaojuzou@163.com.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Zou
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China xiaojuzou@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Liang
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000235:genetics* / Q000378:metabolism*; D050356:Lipid Metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport
chemical_list: D029742:Caenorhabditis elegans Proteins; D050612:Fatty Acid Transport Proteins; D005293:Ferritins; D007501:Iron; D017346:Protein Serine-Threonine Kinases; C540745:Sgk-1 protein, C elegans
keywords: C. elegans; iron; lipid uptake; obesity; serum and glucocorticoid inducible kinase SGK-1