Abstract
Regulation of animal development in response to nutritional cues is an intensely studied problem related to disease and aging. While extensive studies indicated roles of the Target of Rapamycin (TOR) in sensing certain nutrients for controlling growth and metabolism, the roles of fatty acids and lipids in TOR-involved nutrient/food responses are obscure. Caenorhabditis elegans halts postembryonic growth and development shortly after hatching in response to monomethyl branched-chain fatty acid (mmBCFA) deficiency. Here, we report that an mmBCFA-derived sphingolipid, d17iso-glucosylceramide, is a critical metabolite in regulating growth and development. Further analysis indicated that this lipid function is mediated by TORC1 and antagonized by the NPRL-2/3 complex in the intestine. Strikingly, the essential lipid function is bypassed by activating TORC1 or inhibiting NPRL-2/3. Our findings uncover a novel lipid-TORC1 signaling pathway that coordinates nutrient and metabolic status with growth and development, advancing our understanding of the physiological roles of mmBCFAs, ceramides, and TOR.DOI: http://dx.doi.org/10.7554/eLife.00429.001
Highlights
Regulation of animal growth and development in response to nutritional cues is an intensely studied problem (Hietakangas and Cohen, 2009; Zoncu et al, 2011)
Sphingolipids are a class of well-known bioactive lipids (Hannun and Obeid, 2008) that are composed of an aliphatic amino alcohol backbone called the sphingoid base or long chain base (LCB), and usually an N-acylated fatty acid (FA) side chain (Figure 1A)
Disrupting the function of glycosyltransferases that further modify GlcCer does not cause larval arrest (Griffitts et al, 2003). These results suggest that d17iso-glucosylceramide (d17iso-GlcCer) (Figure 1A) may be the lipid molecule that mediates the role of monomethyl branched-chain fatty acid (mmBCFA) and d17iso-SPA in promoting postembryonic growth and development in C. elegans
Summary
Regulation of animal growth and development in response to nutritional cues is an intensely studied problem (Hietakangas and Cohen, 2009; Zoncu et al, 2011). The target of rapamycin (TOR) complexes (TORC1 and TORC2) are known to function in sensing various nutrient signals (Ma and Blenis, 2009; Laplante and Sabatini, 2012; Zoncu et al, 2012), and their roles are connected to growth, metabolism, stress responses, and cancers (Hansen et al, 2008; He and Klionsky, 2009; Howell and Manning, 2011). Energy, and growth factors have been described as nutrient inputs to TOR complexes, roles of lipid molecules as signals to these systems in controlling postembryonic growth and development were not known. It is essential to use whole-animal models to investigate how different signaling systems in different tissues interact to specify decisions regarding postembryonic development and behaviors. In Caenorhabditis elegans, the first larval stage has been established as a model system for the study of animal growth and development in response to food availability. An insulin/IGF-1 receptor signaling (IIS) pathway plays a critical role in the induction of L1 diapause and survival of the developmentally arrested animals
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