論文 - 詳細
| RRC ID | 65326 |
|---|---|
| 著者 | Chamoli M, Goyala A, Tabrez SS, Siddiqui AA, Singh A, Antebi A, Lithgow GJ, Watts JL, Mukhopadhyay A. |
| タイトル | Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction. |
| ジャーナル | Nat Commun |
| Abstract |
The metabolic state of an organism instructs gene expression modalities, leading to changes in complex life history traits, such as longevity. Dietary restriction (DR), which positively affects health and life span across species, leads to metabolic reprogramming that enhances utilisation of fatty acids for energy generation. One direct consequence of this metabolic shift is the upregulation of cytoprotective (CyTP) genes categorized in the Gene Ontology (GO) term of "Xenobiotic Detoxification Program" (XDP). How an organism senses metabolic changes during nutritional stress to alter gene expression programs is less known. Here, using a genetic model of DR, we show that the levels of polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and eicosapentaenoic acid (EPA), are increased following DR and these PUFAs are able to activate the CyTP genes. This activation of CyTP genes is mediated by the conserved p38 mitogen-activated protein kinase (p38-MAPK) pathway. Consequently, genes of the PUFA biosynthesis and p38-MAPK pathway are required for multiple paradigms of DR-mediated longevity, suggesting conservation of mechanism. Thus, our study shows that PUFAs and p38-MAPK pathway function downstream of DR to help communicate the metabolic state of an organism to regulate expression of CyTP genes, ensuring extended life span. |
| 巻・号 | 11(1) |
| ページ | 4865 |
| 公開日 | 2020-9-25 |
| DOI | 10.1038/s41467-020-18690-4 |
| PII | 10.1038/s41467-020-18690-4 |
| PMID | 32978396 |
| PMC | PMC7519657 |
| MeSH | Animals Biochemical Phenomena Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Eicosapentaenoic Acid / analogs & derivatives Fatty Acids, Unsaturated / genetics* Fatty Acids, Unsaturated / metabolism* Gene Expression Regulation* / genetics Gene Knockdown Techniques Linoleic Acid / metabolism Longevity Metabolic Networks and Pathways / genetics Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism p38 Mitogen-Activated Protein Kinases / genetics* p38 Mitogen-Activated Protein Kinases / metabolism* |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 64 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm331 tm789 |