| Title: | Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans |
| Author(s): | Hussey R; Stieglitz J; Mesgarzadeh J; Locke TT; Zhang YK; Schroeder FC; Srinivasan S; |
| Address: | "Department of Molecular Medicine and Department of Neuroscience, The Scripps Research Institute, La Jolla, California, United States of America. Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, United States of America. Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, California, United States of America. Department of Biology, University of California, San Diego, La Jolla, California, United States of America. Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, United States of America" |
| DOI: | 10.1371/journal.pgen.1006806 |
| ISSN/ISBN: | 1553-7404 (Electronic) 1553-7390 (Print) 1553-7390 (Linking) |
| Abstract: | "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 Galpha 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" |
| Keywords: | "Acetylcholine/metabolism Animals Caenorhabditis elegans/genetics/*metabolism Caenorhabditis elegans Proteins/genetics/metabolism Cyclic AMP/metabolism GTP-Binding Protein alpha Subunits, Gi-Go/genetics/metabolism Intestinal Mucosa/metabolism *Lipid Metabo;" |
| Notes: | "MedlineHussey, Rosalind Stieglitz, Jon Mesgarzadeh, Jaleh Locke, Tiffany T Zhang, Ying K Schroeder, Frank C Srinivasan, Supriya eng R01 DK095804/DK/NIDDK NIH HHS/ R01 GM088290/GM/NIGMS NIH HHS/ 2017/05/26 PLoS Genet. 2017 May 18; 13(5):e1006806. doi: 10.1371/journal.pgen.1006806. eCollection 2017 May" |
