Neuronal SKN-1B modulates nutritional signalling pathways and mitochondrial networks to control satiety
| Autor: | Timo Kuerten, Jennifer M. A. Tullet, Ziyun Wu, T. Keith Blackwell, Christopher D Saunter, Ian H. Brown, Maximillian A. Thompson, Isabel Gonçalves Silva, Marina Ezcurra, Alexander Howard, David Weinkove, Nikolaos Tataridas-Pallas |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Nematoda Social Sciences QH426-470 Mitochondrion Biochemistry RNA interference 0302 clinical medicine Transforming Growth Factor beta Animal Cells Medicine and Health Sciences Psychology Energy-Producing Organelles Genetics (clinical) Organism Neurons 0303 health sciences Behavior Animal Animal Behavior Muscles digestive oral and skin physiology Eukaryota Animal Models Mitochondria DNA-Binding Proteins Nucleic acids Genetic interference Experimental Organism Systems Caenorhabditis Elegans Animal Nutritional Physiological Phenomena Epigenetics Sensory Perception Cellular Structures and Organelles Cellular Types Signal Transduction Research Article Sensory system Bioenergetics Biology Research and Analysis Methods Models Biological 03 medical and health sciences Model Organisms Genetics Animals Caenorhabditis elegans Proteins QH426 Molecular Biology Transcription factor Ecology Evolution Behavior and Systematics Nutrition 030304 developmental biology Behavior Organisms Cognitive Psychology Biology and Life Sciences Cell Biology Invertebrates Diet Food Cellular Neuroscience Animal Studies Caenorhabditis RNA Cognitive Science Perception Gene expression Zoology Signalling pathways Neuroscience 030217 neurology & neurosurgery Homeostasis Transcription Factors Hormone |
| Zdroj: | PLoS Genetics PLOS Genetics, 2021, Vol.17(3), pp.e1009358 [Peer Reviewed Journal] PLoS Genetics, Vol 17, Iss 3, p e1009358 (2021) |
| ISSN: | 1553-7404 |
| DOI: | 10.1371/journal.pgen.1009358 |
| Popis: | The feeling of hunger or satiety results from integration of the sensory nervous system with other physiological and metabolic cues. This regulates food intake, maintains homeostasis and prevents disease. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones to control food-related behaviour and physiology. Here we identify a new component of this system, SKN-1B which acts as a central food-responsive node, ultimately controlling satiety and metabolic homeostasis. SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism, respiration and the increased lifespan incurred by dietary restriction. Here we show that SKN-1B acts in two hypothalamus-like ASI neurons to sense food, communicate nutritional status to the organism, and control satiety and exploratory behaviours. This is achieved by SKN-1B modulating endocrine signalling pathways (IIS and TGF-β), and by promoting a robust mitochondrial network. Our data suggest a food-sensing and satiety role for mammalian Nrf proteins. Author summary Deciding when and how much to eat is important for maintaining health and preventing disease. It requires an intricate molecular level of communication between our nervous, physiological, and metabolic systems. These signals stimulate food intake, and afterwards the feeling of satiety which makes us stop eating. We have studied these phenomena using the simple nematode worm C. elegans which has a fully mapped nervous system and quantifiable food-related behaviours. In C. elegans, chemosensory neurons sense food and communicate this to the rest of the animal via hormones to control food-related behaviour and associated physiological changes. Here we identify a new central node of this system, the C. elegans gene SKN-1B, which acts in two sensory neurons to sense food, communicate food-status to the rest of the worm, and control satiety and exploratory behaviours. It does this by altering hormonal signalling (Insulin and Transforming Growth Factor-β), and by promoting a strong mitochondrial network. The mammalian equivalents of SKN-1B are the NF-E2 related transcription factors (Nrfs), which have previously been implicated with metabolism and respiration. Our data suggest a new food-sensing and satiety role for mammalian Nrf proteins. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|