Omega-3 and -6 fatty acids allocate somatic and germline lipids to ensure fitness during nutrient and oxidative stress in Caenorhabditis elegans

Abstract

Animals in nature are continually challenged by periods of feast and famine as resources inevitably fluctuate, and must allocate somatic reserves for reproduction to abate evolutionary pressures. We identify an age-dependent lipid homeostasis pathway in Caenorhabditis elegans that regulates the mobilization of lipids from the soma to the germline, which supports fecundity but at the cost of survival in nutrient-poor and oxidative stress environments. This trade-off is responsive to the levels of dietary carbohydrates and organismal oleic acid and is coupled to activation of the cytoprotective transcription factor SKN-1 in both laboratory-derived and natural isolates of C. elegans. The homeostatic balance of lipid stores between the somatic and germ cells is mediated by arachidonic acid (omega-6) and eicosapentaenoic acid (omega-3) precursors of eicosanoid signaling molecules. Our results describe a mechanism for resource reallocation within intact animals that influences reproductive fitness at the cost of somatic resilience.rade-offs between fecundity and viability fitness components are thought to drive life-history traits when resources are limited (1). In Caenorhabditis elegans, previous studies that removed proliferating germ cells led to an increase in somatic fat (2) and a ∼60% increase in lifespan (3), which is hypothesized to result from the reallocation of germline resources to the soma, promoting survival through enhanced proteostasis (4) and attuned metabolism (5).Although these previous studies are compelling, the use of reproduction-deficient animals confounds the interpretation of their results with regard to trade-off models, and raises the question of how altered reallocation may affect intact animals. During reproduction, somatic resources are deposited to the germline by the actions of vitellogenins (6), which assemble and transport lipids in the form of yolk from the intestine to developing oocytes. The increased survival of germline-defective animals and their accumulation of somatic lipids suggest that the levels of somatic and germline lipids may influence the age-related decline of somatic cell function in postreproductive life (5). The mechanisms that regulate the distribution of energy resources remain elusive, however.SKN-1 is the worm homolog of mammalian Nrf2, a cytoprotective transcription factor that impacts multiple aspects of animal physiology (7). Early work on SKN-1 defined its essential roles in development (8) and oxidative stress responses (9), whereas more recent work has identified a role mediating changes in diet availability and composition (10, 11). In the present study, we examined the SKN-1-mediated dietary adaptation pathways (10-12) of C. elegans and uncovered a sophisticated mechanism for mobilizing somatic lipids to the germline when animals sense stressful environments. This altruistic act by the soma impacts organismal viability to promote fecundity during oxidative and nutrient stress conditions. The universality of oxidative stress responses among aerobic orga...

Advances in the Use of Caenorhabditis Choose in the Nutritional Study of Obesity

“…C. elegans has been successfully reported as an animal model in research related to the characterization of metabolic pathways and storage and release of lipids [41][42][43]. It maintains in its cuticle and in its intestine a range of biosynthetic and catalytic enzymes, as well as reserves of lipids within its hypodermis and intestinal cells [1,42].…”

“…C. elegans has been successfully reported as an animal model in research related to the characterization of metabolic pathways and storage and release of lipids [41][42][43]. It maintains in its cuticle and in its intestine a range of biosynthetic and catalytic enzymes, as well as reserves of lipids within its hypodermis and intestinal cells [1,42]. Using this small animal model, more than 300 genes were proven to cause a reduction in body fat when inactivated, as well as another 100 genes that when inactivated increased or stored fat [33,44].…”

Quantification of Lipid Abundance and Evaluation of Lipid Distribution in <em>Caenorhabditis elegans</em> by Nile Red and Oil Red O Staining

“…Less common is a description of where lipids localize and measured differences in lipid abundance across tissues. However, recent work has revealed that lipid distribution can be as important as lipid accumulation 6 .…”

TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans

“…In mammals, the major oxidative stress transcription factor is the nuclear factor erythroid 2-related factor, Nrf2, one of three Nrf paralogs (Hybertson et al 2011). To ensure efficient surveillance of redox homeostasis, several mechanisms regulate Nrf2, including those that regulate its subcellular localization and protein turnover (Marinho et al 2014).The nematode Caenorhabditis elegans utilizes a functional ortholog of mammalian Nrf proteins, SKN-1, to coordinate its oxidative stress response (Walker et al 2000; found in the regulation of the unfolded protein response and the maintenance of lipid homeostasis (Glover-Cutter et al 2013;Lynn et al 2015;Steinbaugh et al 2015). Similar to Nrf2, SKN-1 regulation is also well studied, and overlapping mechanisms of regulation exist between mammals and worms.…”

“…The nematode Caenorhabditis elegans utilizes a functional ortholog of mammalian Nrf proteins, SKN-1, to coordinate its oxidative stress response (Walker et al 2000; found in the regulation of the unfolded protein response and the maintenance of lipid homeostasis (Glover-Cutter et al 2013;Lynn et al 2015;Steinbaugh et al 2015). Similar to Nrf2, SKN-1 regulation is also well studied, and overlapping mechanisms of regulation exist between mammals and worms.…”