Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans.
It is now established that the central nervous system plays an important role in regulating whole body metabolism and energy balance. However, the extent to which sensory systems relay environmental information to modulate metabolic events in peripheral tissues has remained poorly understood. In add...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-05-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5456406?pdf=render |
| _version_ | 1811334837439561728 |
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| author | Rosalind Hussey Jon Stieglitz Jaleh Mesgarzadeh Tiffany T Locke Ying K Zhang Frank C Schroeder Supriya Srinivasan |
| author_facet | Rosalind Hussey Jon Stieglitz Jaleh Mesgarzadeh Tiffany T Locke Ying K Zhang Frank C Schroeder Supriya Srinivasan |
| author_sort | Rosalind Hussey |
| collection | DOAJ |
| description | It is now established that the central nervous system plays an important role in regulating whole body metabolism and energy balance. However, the extent to which sensory systems relay environmental information to modulate metabolic events in peripheral tissues has remained poorly understood. In addition, it has been challenging to map the molecular mechanisms underlying discrete sensory modalities with respect to their role in lipid metabolism. In previous work our lab has identified instructive roles for serotonin signaling as a surrogate for food availability, as well as oxygen sensing, in the control of whole body metabolism. In this study, we now identify a role for a pair of pheromone-sensing neurons in regulating fat metabolism in C. elegans, which has emerged as a tractable and highly informative model to study the neurobiology of metabolism. A genetic screen revealed that GPA-3, a member of the Gα family of G proteins, regulates body fat content in the intestine, the major metabolic organ for C. elegans. Genetic and reconstitution studies revealed that the potent body fat phenotype of gpa-3 null mutants is controlled from a pair of neurons called ADL(L/R). We show that cAMP functions as the second messenger in the ADL neurons, and regulates body fat stores via the neurotransmitter acetylcholine, from downstream neurons. We find that the pheromone ascr#3, which is detected by the ADL neurons, regulates body fat stores in a GPA-3-dependent manner. We define here a third sensory modality, pheromone sensing, as a major regulator of body fat metabolism. The pheromone ascr#3 is an indicator of population density, thus we hypothesize that pheromone sensing provides a salient 'denominator' to evaluate the amount of food available within a population and to accordingly adjust metabolic rate and body fat levels. |
| first_indexed | 2024-04-13T17:15:05Z |
| format | Article |
| id | doaj.art-deb18dd8de53439c93d1d5b5ab9440e3 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-13T17:15:05Z |
| publishDate | 2017-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-deb18dd8de53439c93d1d5b5ab9440e32022-12-22T02:38:10ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-05-01135e100680610.1371/journal.pgen.1006806Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans.Rosalind HusseyJon StieglitzJaleh MesgarzadehTiffany T LockeYing K ZhangFrank C SchroederSupriya SrinivasanIt is now established that the central nervous system plays an important role in regulating whole body metabolism and energy balance. However, the extent to which sensory systems relay environmental information to modulate metabolic events in peripheral tissues has remained poorly understood. In addition, it has been challenging to map the molecular mechanisms underlying discrete sensory modalities with respect to their role in lipid metabolism. In previous work our lab has identified instructive roles for serotonin signaling as a surrogate for food availability, as well as oxygen sensing, in the control of whole body metabolism. In this study, we now identify a role for a pair of pheromone-sensing neurons in regulating fat metabolism in C. elegans, which has emerged as a tractable and highly informative model to study the neurobiology of metabolism. A genetic screen revealed that GPA-3, a member of the Gα family of G proteins, regulates body fat content in the intestine, the major metabolic organ for C. elegans. Genetic and reconstitution studies revealed that the potent body fat phenotype of gpa-3 null mutants is controlled from a pair of neurons called ADL(L/R). We show that cAMP functions as the second messenger in the ADL neurons, and regulates body fat stores via the neurotransmitter acetylcholine, from downstream neurons. We find that the pheromone ascr#3, which is detected by the ADL neurons, regulates body fat stores in a GPA-3-dependent manner. We define here a third sensory modality, pheromone sensing, as a major regulator of body fat metabolism. The pheromone ascr#3 is an indicator of population density, thus we hypothesize that pheromone sensing provides a salient 'denominator' to evaluate the amount of food available within a population and to accordingly adjust metabolic rate and body fat levels.http://europepmc.org/articles/PMC5456406?pdf=render |
| spellingShingle | Rosalind Hussey Jon Stieglitz Jaleh Mesgarzadeh Tiffany T Locke Ying K Zhang Frank C Schroeder Supriya Srinivasan Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans. PLoS Genetics |
| title | Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans. |
| title_full | Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans. |
| title_fullStr | Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans. |
| title_full_unstemmed | Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans. |
| title_short | Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans. |
| title_sort | pheromone sensing neurons regulate peripheral lipid metabolism in caenorhabditis elegans |
| url | http://europepmc.org/articles/PMC5456406?pdf=render |
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