Reference - Detail
| RRC ID | 53249 |
|---|---|
| Author | Wang H, Jiang X, Wu J, Zhang L, Huang J, Zhang Y, Zou X, Liang B. |
| Title | Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans. |
| Journal | Genetics |
| 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. |
| Volume | 203(1) |
| Pages | 241-53 |
| Published | 2016-5-1 |
| DOI | 10.1534/genetics.116.186742 |
| PII | genetics.116.186742 |
| PMID | 27017620 |
| PMC | PMC4858777 |
| MeSH | Adiposity / genetics* Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Disease Models, Animal Fatty Acid Transport Proteins / genetics Fatty Acid Transport Proteins / metabolism Ferritins / genetics* Ferritins / metabolism Gene Expression Regulation* Iron / metabolism* Iron Overload / genetics* Iron Overload / metabolism* Lipid Metabolism Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Protein Transport |
| IF | 4.015 |
| Times Cited | 13 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm3232 |