Systemic regulation of starvation response in Caenorhabditis elegans

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Genes & development (Impact Factor: 10.8). 02/2009; 23(1):12-7. DOI: 10.1101/gad.1723409
Source: PubMed


When the supply of environmental nutrients is limited, multicellular animals can make both physiological and behavioral changes so as to cope with nutrient starvation. Although physiological and behavioral effects of starvation are well known, the mechanisms by which animals sense starvation systemically remain elusive. Furthermore, what constituent of food is sensed and how it modulates starvation response is still poorly understood. In this study, we use a starvation-hypersensitive mutant to identify molecules and mechanisms that modulate starvation signaling. We found that specific amino acids could suppress the starvation-induced death of gpb-2 mutants, and that MGL-1 and MGL-2, Caenorhabditis elegans homologs of metabotropic glutamate receptors, were involved. MGL-1 and MGL-2 acted in AIY and AIB neurons, respectively. Treatment with leucine suppressed starvation-induced stress resistance and life span extension in wild-type worms, and mutation of mgl-1 and mgl-2 abolished these effects of leucine. Taken together, our results suggest that metabotropic glutamate receptor homologs in AIY and AIB neuron may modulate a systemic starvation response, and that C. elegans senses specific amino acids as an anti-hunger signal.

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    • "Furthermore, daf-2/InsR, age-1/PI3K, and other mutants that extend lifespan further extend heat resistance during L1 arrest, consistent with a common genetic basis between lifespan and starvation-induced heat resistance (Munoz and Riddle 2003). Oxidative stress resistance is also increased during L1 arrest (Weinkove et al. 2006; Kang and Avery 2009b). Again, increased resistance to oxidative stress requires daf-16/FOXO as well as daf- 18/PTEN, and mutations affecting age-1/PI3K further increase resistance, suggesting a common genetic basis between lifespan and starvation-induced oxidative stress resistance (Weinkove et al. 2006). "
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    ABSTRACT: It is widely appreciated that larvae of the nematode Caenorhabditis elegans arrest development by forming dauer larvae in response to multiple unfavorable environmental conditions. C. elegans larvae can also reversibly arrest development earlier, during the first larval stage (L1), in response to starvation. "L1 arrest" (also known as "L1 diapause") occurs without morphological modification but is accompanied by increased stress resistance. Caloric restriction and periodic fasting can extend adult lifespan, and developmental models are critical to understanding how the animal is buffered from fluctuations in nutrient availability, impacting lifespan. L1 arrest provides an opportunity to study nutritional control of development. Given its relevance to aging, diabetes, obesity and cancer, interest in L1 arrest is increasing, and signaling pathways and gene regulatory mechanisms controlling arrest and recovery have been characterized. Insulin-like signaling is a critical regulator, and it is modified by and acts through microRNAs. DAF-18/PTEN, AMP-activated kinase and fatty acid biosynthesis are also involved. The nervous system, epidermis, and intestine contribute systemically to regulation of arrest, but cell-autonomous signaling likely contributes to regulation in the germline. A relatively small number of genes affecting starvation survival during L1 arrest are known, and many of them also affect adult lifespan, reflecting a common genetic basis ripe for exploration. mRNA expression is well characterized during arrest, recovery, and normal L1 development, providing a metazoan model for nutritional control of gene expression. In particular, post-recruitment regulation of RNA polymerase II is under nutritional control, potentially contributing to a rapid and coordinated response to feeding. The phenomenology of L1 arrest will be reviewed, as well as regulation of developmental arrest and starvation survival by various signaling pathways and gene regulatory mechanisms.
    Full-text · Article · Jul 2013 · Genetics
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    • "Increased pharyngeal pumping during starvation (You et al., 2006), and activation of autophagy in pharyngeal cells (Kang et al., 2007) both require cholinergic muscarinic signalling. Autophagy was suppressed by addition of specific amino acids, activating metabotropic glutamatergic receptors in the AIY and AIB interneurones, and affecting the pharynx, presumably through the release of yet unidentified neuropeptides (Kang and Avery, 2009). AIB neurones were also shown to regulate roaming and quiescence behaviours in response to food (Bendena et al., 2008), and both AIB and AIY were shown to regulate feeding-related behaviours downstream to signals from the AWC chemosensory neurones, which are the main regulators of food-seeking behaviour (Bargmann, 2006). "
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    ABSTRACT: Symbiosis, the living together of unlike organisms, such as between microbes and their multicellular eukaryotic hosts, can be categorized as parasitic, commensal or mutualistic. The establishment of symbiosis and the outcome of microbe-host interactions are dictated largely by both microbe- and host-derived factors. Over the last decade, the nematode Caenorhabditis elegans has provided a facile experimental system to study such interactions, with parasitic interactions being the primary focus. The myriad of genetic and molecular tools available has made C. elegans a powerful model system to interrogate the interactions between a host and its pathogens, and has provided a greater understanding of the molecular underpinnings of these interactions, many of which were found to be conserved across other taxa. Commensal and mutualistic interactions between worms and their microbes, although less studied, have the potential to enhance our understanding of genetic and molecular features underlying host-microbe interactions. Here, we highlight new insights obtained in delineating the signalling pathways that function within and between host cells in combating assaults from extracellular and intracellular pathogens. We also discuss potential new insights that could be gained from further studies into commensal and mutualistic relationships between nematodes and microbes.
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    • "Therefore, C17iso levels may reflect the levels of essential dietary amino acids. A recent study found that dietary leucine specifically rescues starvation-induced death in gpb-2 mutants, and that dietary leucine suppresses starvation-induced stress and lifespan extension in wild-type worms [38], demonstrating the importance of this amino acid in regulating dietary responses in C. elegans. Future studies investigating the precise amounts of particular amino acid species in the dietary E. coli strains as well as in the worms feeding on them may provide further insight on the role of leucine in the regulation of fat storage. "
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    ABSTRACT: The nematode Caenorhabditis elegans has emerged as an important model for studies of the regulation of fat storage. C. elegans feed on bacteria, and various strains of E. coli are commonly used in research settings. However, it is not known whether particular bacterial diets affect fat storage and metabolism. Fat staining of fixed nematodes, as well as biochemical analysis of lipid classes, revealed considerable differences in fat stores in C. elegans growing on four different E. coli strains. Fatty acid composition and carbohydrate levels differ in the E. coli strains examined in these studies, however these nutrient differences did not appear to have a causative effect on fat storage levels in worms. Analysis of C. elegans strains carrying mutations disrupting neuroendocrine and other fat-regulatory pathways demonstrated that the intensity of Nile Red staining of live worms does not correlate well with biochemical methods of fat quantification. Several neuroendocrine pathway mutants and eating defective mutants show higher or lower fat storage levels than wild type, however, these mutants still show differences in fat stores when grown on different bacterial strains. Of all the mutants tested, only pept-1 mutants, which lack a functional intestinal peptide transporter, fail to show differential fat stores. Furthermore, fatty acid analysis of triacylglycerol stores reveals an inverse correlation between total fat stores and the levels of 15-methylpalmitic acid, derived from leucine catabolism. These studies demonstrate that nutritional cues perceived in the intestine regulate fat storage levels independently of neuroendocrine cues. The involvement of peptide transport and the accumulation of a fatty acid product derived from an amino acid suggest that specific peptides or amino acids may provide nutritional signals regulating fat metabolism and fat storage levels.
    Full-text · Article · Oct 2009 · PLoS ONE
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