Oxygen-sensing neurons reciprocally regulate peripheral lipid metabolism via neuropeptide signaling in Caenorhabditis elegans

• DOI: 10.1371/journal.pgen.1007305
• Publication Date: 2018-03-26T17:26:21Z
• Authors: Rosalind Hussey; Nicole K. Littlejohn; Emily Witham; Erik Vanstrum; Jaleh Mesgarzadeh; Harkaranveer Rata...; Supriya Srinivasan
• Keywords: Caenorhabditis elegans/metabolism; Sensory Receptor Cells/metabolism; 0303 health sciences; Sensory Receptor Cells; Neuropeptides; Cell Communication; QH426-470; Oxygen/metabolism; Lipid Metabolism; Neuropeptides/metabolism; Oxygen; 03 medical and health sciences; Guanylate Cyclase; Genetics; Animals; Intestinal Mucosa; Guanylate Cyclase/metabolism; Caenorhabditis elegans; Intestinal Mucosa/metabolism; Research Article; Signal Transduction

AbstractThe mechanisms by which the sensory environment instructs metabolic homeostasis remains poorly understood. In this report, we show that oxygen, a potent environmental signal, is an important regulator of whole body lipid metabolism.C. elegansoxygen-sensing neurons reciprocally regulate peripheral lipid metabolism under normoxia in the following way: under high oxygen and food absence, URX sensory neurons are activated, and stimulate fat loss in the intestine, the major metabolic organ forC. elegans. Under lower oxygen conditions or when food is present, the BAG sensory neurons respond by repressing the resting properties of the URX neurons. A genetic screen to identify modulators of this effect led to the identification of a BAG-neuron-specific neuropeptide called FLP-17, whose cognate receptor EGL-6 functions in URX neurons. Thus, BAG sensory neurons counterbalance the metabolic effect of tonically active URX neurons via neuropeptide communication. The combined regulatory actions of these neurons serve to precisely tune the rate and extent of fat loss, to the availability of food and oxygen.