title: AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators.
abstract: Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co-activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases.
authors.affiliation: Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Mexico City, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Moreno-Arriola
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Mexico City, Mexico.
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Hafidi
authors.affiliation: Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Mexico City, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ortega-Cuéllar
authors.affiliation: Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Mexico City, Mexico.
authors.forename: Karla
authors.initials: K
authors.lastname: Carvajal
mesh_terms: D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D008687:Metformin / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; C571065:MDT-15 protein, C elegans; C505159:NHR-49 protein, C elegans; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D012265:Ribonucleotides; C513283:SBP-1 protein, C elegans; D014157:Transcription Factors; D019344:Lactic Acid; D000620:Aminoimidazole Carboxamide; D008687:Metformin; D017346:Protein Serine-Threonine Kinases; C510541:AAK-2 protein, C elegans; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose; D010100:Oxygen
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