Emerging roles for specific fatty acids in developmental processes

Vrablik, Tracy; Watts, Jennifer L.

doi:10.1101/gad.190777.112

Cited by 42 publications

(34 citation statements)

References 38 publications

(43 reference statements)

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“…There is no known mode of action for ME, however it likely disturbs the organization of the actin cytoskeleton (Opalski et al, 2006). Both inhibition of 3-keto reductase and disruption of the actin dynamics may indirectly affect mitochondrial membrane fluidity and function (Breitenbach et al, 2005;Vrablik and Watts, 2012). Both CY, FE and ME displayed similar LC50 values (∼25 μM) against cortical neurons viability when they were exposed to the fungicides for 7 days in vitro, despite the fact that CY was much more potent than FE and ME in inducing mitochondrial membrane depolarization (Fig.…”

Section: Discussionmentioning

confidence: 99%

Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons

Regueiro

Olguín

Simal‐Gándara

et al. 2015

Environmental Research

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Fungicides are crucial for food protection as well as for the production of crops of suitable quality and quantity to provide a viable economic return. Like other pesticides, fungicides are widely sprayed on agricultural land, especially in wine-growing areas, from where they can move-off after application. Furthermore, residues of these agrochemicals can remain on crops after harvest and even after some food processing operations, being a major exposure pathway. Although a relatively low toxicity has been claimed for this kind of compounds, information about their neurotoxicity is still scarce. In the present study, nine fungicides recently approved for agricultural uses in the EU - ametoctradin, boscalid, cyazofamid, dimethomorph, fenhexamid, kresoxim-methyl, mepanipyrim, metrafenone and pyraclostrobin - have been evaluated for their toxicity in primary cultured mouse cortical neurons. Exposure to 0.1-100µM for 7 days in vitro resulted in a dose-dependent toxicity in the MTT cell viability assay. Strobilurin fungicides kresoxim-methyl (KR) and pyraclostrobin (PY) were the most neurotoxic compounds (lethal concentration 50 were in the low micromolar and nanomolar levels, respectively) causing a rapid raise in intracellular calcium [Ca(2+)]i and strong depolarization of mitochondrial membrane potential. KR- and PY-induced cell death was reversed by the calcium channels blockers MK-801 and verapamil, suggesting that calcium entry through NMDA receptors and voltage-operated calcium channels are involved in KR- and PY-induced neurotoxicity. These results highlight the need for further evaluation of their neurotoxic effects in vivo.

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Section: Discussionmentioning

confidence: 99%

Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons

Regueiro

Olguín

Simal‐Gándara

et al. 2015

Environmental Research

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“…Lipids continue to emerge as a class of molecules that affect behavior, growth, and organismal survival, not only because of their energetic value, but also because of their structural and signaling functions (Vrablik and Watts 2012). In C. elegans, v-3/6 PUFAs are required for normal development and neural function (Watts et al 2003;Kahn-Kirby et al 2004).…”

Section: Discussionmentioning

confidence: 99%

ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy

et al. 2013

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Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing C. elegans culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs.

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“…Isotope labeling experiments show that in wild-type animals de novo lipogenesis accounts for less than 10% of stored body fat, whereas defects in insulin signaling increase that number to approximately 25% (21). Fatty acid desaturation in C. elegans appears to be a strategy to diversify the lipidome and provide a plethora of substrates for signal transduction pathways that control organismal physiology (22-24). Nuclear magnetic resonance studies reveal that a novel form of pheromones called ascarosides are composed of long-chain fatty acids (26 carbon and up), anchored by a sugar backbone.…”

Section: Composition Of Body Fatmentioning

confidence: 99%

Regulation of Body Fat in Caenorhabditis elegans

Srinivasan

2015

Annu. Rev. Physiol.

102

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Studies conducted in C. elegans over the last decade highlight the ancient and complex origins of body fat regulation. In this critical review, I introduce the major functional approaches used to study energy balance and body fat, the lipid composition of C. elegans, the regulation of cellular fat metabolism and its transcriptional control. Next I describe the influence of the sensory nervous system on body fat and the major regulatory mechanisms that couple food perception in the nervous system with the production of energy via fat metabolism. The final section describes the opportunities for the discovery of neuroendocrine factors that control communication between the nervous system and the metabolic tissues. The coming years are expected to reveal a wealth of information on the neuroendocrine control of body fat in C. elegans.

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Emerging roles for specific fatty acids in developmental processes

Cited by 42 publications

References 38 publications

Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons

Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons

ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy

Regulation of Body Fat in Caenorhabditis elegans

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