Abstract
The mechanisms by which the sensory environment influences 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. elegans oxygen-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 for C. 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, and provides an interesting example of the myriad mechanisms underlying homeostatic control.
Highlights
The central nervous system plays a critical role in regulating whole body energy balance
BAG and URX neurons reciprocally regulate lipid metabolism via neuropeptide signaling in C. elegans
Food intake (Fig 1C) and locomotor rates [17] are indistinguishable between wild-type and gcy-33 mutants, suggesting that differences in the metabolism of fat stores underlies the fat phenotype of gcy-33 mutants. gcy-33 mutants are defective in the behavioral and neuronal responses to low oxygen, which are encoded by the BAG neurons [17, 19]
Summary
The central nervous system plays a critical role in regulating whole body energy balance. At least 3 discrete sensory inputs: food availability [9,10,11], population density [12] and environmental oxygen [13] are relayed from chemosensory neurons to the intestine. These sensory inputs control the duration and magnitude of fat loss, effectively coupling environmental information with body fat metabolism via neuroendocrine hormones. The molecular and neuroendocrine mechanisms by which sensory information is relayed from the nervous system to the intestine has the tremendous potential to shed light on the interaction between genetic mechanisms and environmental conditions in controlling lipid metabolism
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