Developmental Ethanol Exposure Leads to Dysregulation of Lipid Metabolism and Oxidative Stress in <i>Drosophila</i>

Logan-Garbisch, Theresa; Bortolazzo, Anthony; Luu, Peter; Ford, Audrey; Do, David; Khodabakhshi, Payam; French, Rachael L.

doi:10.1534/g3.114.015040

Cited by 46 publications

(42 citation statements)

References 56 publications

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“…Therefore, the upregulation of uro under MD conditions might not be directly linked to dietary urea. uro is involved in many stress-related pathways, such as exposure to ethanol (Logan-Garbisch et al, 2014) or oxidative stress (Terhzaz et al, 2010). Other studies have also reported an upregulation of uro in cold-exposed Drosophila adults (Zhang et al, 2011;Boardman et al, 2017); therefore, this gene probably has multiple functions related to stress-tolerance mechanisms.…”

Section: Discussionmentioning

confidence: 96%

Hormesis-like effect of mild larval crowding on thermotolerance inDrosophilaflies

Henry

Renault

Colinet

2017

Journal of Experimental Biology

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Crowding is a complex stress that can affect organisms' physiology, especially through decreased food quality and accessibility. Here, we evaluated the effect of larval density on several biological traits of An increasing gradient, from 1 to 1000 eggs per milliliter of food, was used to characterize life-history traits variations. Crowded conditions resulted in striking decreases of fresh mass (up to 6-fold) and viability, as well as delayed development. Next, we assessed heat and cold tolerance in L3 larvae reared at three selected larval densities: low (LD, 5 eggs ml), medium (MD, 60 eggs ml) and high (HD, 300 eggs ml). LT values of MD and, to a lesser extent, HD larvae were repeatedly higher than those from LD larvae, under both heat and cold stress. We investigated potential physiological correlates associated with this density-dependent thermotolerance shift. No marked pattern could be drawn from the expression of stress-related genes. However, a metabolomic analysis differentiated the metabotypes of the three density levels, with potential candidates associated with this clustering (e.g. glucose 6-phosphate, GABA, sugars and polyols). Under HD, signs of oxidative stress were noted but not confirmed at the transcriptional level. Finally, urea, a common metabolic waste, was found to accumulate substantially in food from MD and HD larvae. When supplemented in food, urea stimulated cold tolerance but reduced heat tolerance in LD larvae. This study highlights that larval crowding is an important environmental parameter that induces drastic consequences on flies' physiology and can affect thermotolerance in a density-specific way.

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Section: Discussionmentioning

confidence: 96%

Hormesis-like effect of mild larval crowding on thermotolerance inDrosophilaflies

Henry

Renault

Colinet

2017

Journal of Experimental Biology

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“…| 885 localized within glial cells. In contrast, it has been described that accumulation of excess fatty acids in cellular triacylglyceride stores may be protective against lipotoxicity (Listenberger et al, 2003;Logan-Garbisch et al, 2014). Moreover, from our analysis, it seems that triacylglycerides accumulated into LDs are unsaturated lipids due to their high affinity for osmium tetroxide (De Martino, Natali, Bruni, & Accinni, 1968;Digel, Ehehalt, & F€ ullekrug, 2010;Fujimoto et al, 2013).…”

Section: Discussionmentioning

confidence: 50%

“…In normal conditions, the primary function of LDs is to store triacylglycerols and sterol derivatives, which can be mobilized to fuel ß-oxidation for energy generation and to provide membrane precursors (Goodman, 2009;Guo, Cordes, Farese, & Walther, 2009). In contrast, it has been described that accumulation of excess fatty acids in cellular triacylglyceride stores may be protective against lipotoxicity (Listenberger et al, 2003;Logan-Garbisch et al, 2014). Increased number of LDs has been shown in experimental models of cellular stress such as nutrient deprivation (Cabodevilla et al, 2013) and in metabolic or mitochondrial diseases (Greenberg et al, 2011;Bayat et al, 2012;Golla, Ren, Malloy, & Pascual, 2017).…”

Section: Discussionmentioning

confidence: 99%

Glial lipid droplets and neurodegeneration in a Drosophila model of complex I deficiency

Cabirol-Pol

Khalil

Rival

et al. 2017

Glia

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Mitochondrial defects associated with respiratory chain complex I deficiency lead to heterogeneous fatal syndromes. While the role of NDUFS8, an essential subunit of the core assembly of the complex I, is established in mitochondrial diseases, the mechanisms underlying neuropathology are poorly understood. We developed a Drosophila model of NDUFS8 deficiency by knocking down the expression of its fly homologue in neurons or in glial cells. Downregulating ND23 in neurons resulted in shortened lifespan, and decreased locomotion. Although total brain ATP levels were decreased, histological analysis did not reveal any signs of neurodegeneration except for photoreceptors of the retina. Interestingly, ND23 deficiency-associated phenotypes were rescued by overexpressing the glucose transporter hGluT3 demonstrating that boosting glucose metabolism in neurons was sufficient to bypass altered mitochondrial functions and to confer neuroprotection. We then analyzed the consequences of ND23 knockdown in glial cells. In contrast to neuronal knockdown, loss of ND23 in glia did not lead to significant behavioral defects nor to reduced lifespan, but induced brain degeneration, as visualized by numerous vacuoles found all over the nervous tissue. This phenotype was accompanied by the massive accumulation of lipid droplets at the cortex-neuropile boundaries, suggesting an alteration of lipid metabolism in glia. These results demonstrate that complex I deficiency triggers metabolic alterations both in neurons and glial cells which may contribute to the neuropathology.

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“…We explored the glutathione synthetase region (containing Gss1 and Gss2), which is just one example among hundreds in modENCODE that likely suffer from misleading annotations. A tandem duplication present in ISO1 has created two copies of Gss1 and Gss2, which are associated with toxin metabolism and linked to tolerance to arsenic (Ortiz et al 2009) and ethanol induced oxidative stress (Logan-Garbisch et al 2015). While this duplication segregates at high frequency in DSPR strains (9/13), it is absent in Oregon-R ( Fig.…”

Section: Functional Structural Variation At Mapped Qtlmentioning

confidence: 99%

Structural variants exhibit allelic heterogeneity and shape variation in complex traits

Chakraborty

Emerson

et al. 2018

Preprint

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Despite extensive effort to reveal the genetic basis of complex phenotypic variation, studies typically explain only a fraction of trait heritability. It has been hypothesized that individually rare hidden structural variants (SVs) could account for a significant fraction of variation in complex traits. To investigate this hypothesis, we assembled 14Drosophila melanogaster genomes and systematically identified more than 20,000 euchromatic SVs, of which ~40% are invisible to high specificity short read genotyping approaches. SVs are common in Drosophila genes, with almost one third of diploid individuals harboring an SV in genes larger than 5kb, and nearly a quarter harboring multiple SVs in genes larger than 10kb. We show that SV alleles are rarer than amino acid polymorphisms, implying that they are more strongly deleterious. A number of functionally important genes harbor previously hidden structural variants that likely affect complex phenotypes (e.g., Cyp6g1, Drsl5, Cyp28d1&2, InR, and Gss1&2).Furthermore, SVs are overrepresented in quantitative trait locus candidate genes from eight Drosophila Synthetic Population Resource (DSPR) mapping experiments. We conclude that SVs are pervasive in genomes, are frequently present as heterogeneous allelic series, and can act as rare alleles of large effect.

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Developmental Ethanol Exposure Leads to Dysregulation of Lipid Metabolism and Oxidative Stress in Drosophila

Cited by 46 publications

References 56 publications

Hormesis-like effect of mild larval crowding on thermotolerance inDrosophilaflies

Hormesis-like effect of mild larval crowding on thermotolerance inDrosophilaflies

Glial lipid droplets and neurodegeneration in a Drosophila model of complex I deficiency

Structural variants exhibit allelic heterogeneity and shape variation in complex traits

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