Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction
| Autor: | Manish Chamoli, Gordon J. Lithgow, Anita Goyala, Arnab Mukhopadhyay, Jennifer L. Watts, Syed Shamsh Tabrez, Anupama Singh, Adam Antebi, Atif Ahmed Siddiqui |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell signaling Biochemical Phenomena Science media_common.quotation_subject Longevity General Physics and Astronomy Biology Protein Serine-Threonine Kinases p38 Mitogen-Activated Protein Kinases General Biochemistry Genetics and Molecular Biology Article Linoleic Acid 03 medical and health sciences 0302 clinical medicine Genetic model Gene expression Animals Lipid signalling lcsh:Science Caenorhabditis elegans Caenorhabditis elegans Proteins Gene media_common chemistry.chemical_classification Regulation of gene expression Multidisciplinary General Chemistry Nutrient signalling Eicosapentaenoic acid Cell biology Gene regulation 030104 developmental biology chemistry Eicosapentaenoic Acid Gene Expression Regulation Gene Knockdown Techniques Fatty Acids Unsaturated lcsh:Q 030217 neurology & neurosurgery Metabolic Networks and Pathways Polyunsaturated fatty acid Cell signalling |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nat Commun |
| ISSN: | 2041-1723 |
| Popis: | 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. Metabolic reprogramming during Dietary Restriction (DR) activates cytoprotective gene expression. Here the authors show that PUFAs generated during DR signal via the p38-MAPK pathway to enhance cytoprotective gene expression, contributing to increased longevity. |
| Databáze: | OpenAIRE |
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