Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans

• Published in: PLoS genetics Vol. 13; no. 5; p. e1006806
• Main Authors: Hussey, Rosalind, Stieglitz, Jon, Mesgarzadeh, Jaleh, Locke, Tiffany T, Zhang, Ying K, Schroeder, Frank C, Srinivasan, Supriya
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.05.2017; Public Library of Science (PLoS)
• Subjects: Acetylcholine; Acetylcholine - metabolism; Animals; Biology and Life Sciences; Body fat; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Central nervous system; Cyclic AMP; Cyclic AMP - metabolism; Energy balance; Energy metabolism; Fat metabolism; Food availability; Genes; Genetic aspects; Genetic screening; GTP-Binding Protein alpha Subunits, Gi-Go - genetics; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; Information systems; Intestine; Intestines - metabolism; Lipid Metabolism; Medicine and Health Sciences; Metabolic rate; Molecular modelling; Nematodes; Nervous system; Neurons; Neurosciences; Oxygen; Pheromones - metabolism; Physiological aspects; Population density; Research and Analysis Methods; Second Messenger Systems; Sensory Receptor Cells - metabolism; Sensory systems; Serotonin; Stores; Worms; La Jolla California; United States > US; California
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006806

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.