Neural and molecular dissection of a C. elegans sensory circuit that regulates fat and feeding |
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Authors: | Greer Elisabeth R Pérez Carissa L Van Gilst Marc R Lee Brian H Ashrafi Kaveh |
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Institution: | 1Department of Physiology, 600 16th Street, Mission Bay Campus Box 2240, University of California, San Francisco, CA, 94158-2517, USA;2Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA;3Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA |
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Abstract: | A major challenge in understanding energy balance is deciphering the neural and molecular circuits that govern behavioral, physiological, and metabolic responses of animals to fluctuating environmental conditions. The neurally expressed TGF-β ligand DAF-7 functions as a gauge of environmental conditions to modulate energy balance in C. elegans. We show that daf-7 signaling regulates fat metabolism and feeding behavior through a compact neural circuit that allows for integration of multiple inputs and the flexibility for differential regulation of outputs. In daf-7 mutants, perception of depleting food resources causes fat accumulation despite reduced feeding rate. This fat accumulation is mediated, in part, through neural metabotropic glutamate signaling and upregulation of peripheral endogenous biosynthetic pathways that direct energetic resources into fat reservoirs. Thus, neural perception of adverse environmental conditions can promote fat accumulation without a concomitant increase in feeding rate. |
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Keywords: | HUMDISEASE MOLNEURO |
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