Drosophila lacks C20 and C22 PUFAs

Shen, Li; Lai, Chao‐Qiang; Feng, Xiaodong; Parnell, Laurence D.; Wan, Jian; Wang, Jing Dong; Li, Duo; Ordovas, José M.; Kang, Jing

doi:10.1194/jlr.m008524

Cited by 99 publications

(95 citation statements)

References 14 publications

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“…In particular, docosahexaenoic acid (DHA), a fatty acid essential for cerebral function in mammals, has been extensively implicated in amyloid production and toxicity, the supplementation potential of which has been previously demonstrated in AD models (Florent-Béchard et al, 2009). However, analyses of the fatty acids composition of Drosophila has revealed a complete lack of C20 and C22 PUFAs such as DHA, and no genes encoding for Δ-6/Δ-5 desaturases, the key enzymes for the synthesis of C20/C22 PUFA, were detected in Drosophila (Shen et al, 2010). Therefore, we surmised that the effects of HSM on neuroprotection against amyloid would be mediated by other PUFAs, with the exception of DHA.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Hempseed Meal Intake and Linoleic Acid on Drosophila Models of Neurodegenerative Diseases and Hypercholesterolemia

Lee

Park

Han

et al. 2011

Molecules and Cells

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Hempseed is rich in polyunsaturated fatty acids (PUFAs), which have potential as therapeutic compounds for the treatment of neurodegenerative and cardiovascular disease. However, the effect of hempseed meal (HSM) intake on the animal models of these diseases has yet to be elucidated. In this study, we assessed the effects of the intake of HSM and PUFAs on oxidative stress, cytotoxicity and neurological phenotypes, and cholesterol uptake, using Drosophila models. HSM intake was shown to reduce H 2 O 2 toxicity markedly, indicating that HSM exerts a profound antioxidant effect. Meanwhile, intake of HSM, as well as linoleic or linolenic acids (major PUFA components of HSM) was shown to ameliorate Aβ42-induced eye degeneration, thus suggesting that these compounds exert a protective effect against Aβ42 cytotoxicity. On the contrary, locomotion and longevity in the Parkinson's disease model and eye degeneration in the Huntington's disease model were unaffected by HSM feeding. Additionally, intake of HSM or linoleic acid was shown to reduce cholesterol uptake significantly. Moreover, linoleic acid intake has been shown to delay pupariation, and cholesterol feeding rescued the linoleic acid-induced larval growth delay, thereby indicating that linoleic acid acts antagonistically with cholesterol during larval growth. In conclusion, our results indicate that HSM and linoleic acid exert inhibitory effects on both Aβ42 cytotoxicity and cholesterol uptake, and are potential candidates for the treatment of Alzheimer's disease and cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

The Effects of Hempseed Meal Intake and Linoleic Acid on Drosophila Models of Neurodegenerative Diseases and Hypercholesterolemia

Lee

Park

Han

et al. 2011

Molecules and Cells

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“…C20 and C22 polyunsaturated fatty acids are absent in Drosophila (Shen et al, 2010). To further understand how Acsl affects the fatty acid metabolism, we analyzed fatty acids in thirdinstar larval brains of Acsl KO /Acsl 05847 mutants.…”

Section: Acsl Regulates Brain Fatty Acid Compositionmentioning

confidence: 99%

Acsl, the Drosophila ortholog of intellectual-disability-related ACSL4, inhibits synaptic growth by altered lipids

Huang

Lam

et al. 2016

Journal of Cell Science

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Nervous system development and function are tightly regulated by metabolic processes, including the metabolism of lipids such as fatty acids. Mutations in long-chain acyl-CoA synthetase 4 (ACSL4) are associated with non-syndromic intellectual disabilities. We previously reported that Acsl, the Drosophila ortholog of mammalian ACSL3 and ACSL4, inhibits neuromuscular synapse growth by suppressing bone morphogenetic protein (BMP) signaling. Here, we report that Acsl regulates the composition of fatty acids and membrane lipids, which in turn affects neuromuscular junction (NMJ) synapse development. Acsl mutant brains had a decreased abundance of C16:1 fatty acyls; restoration of Acsl expression abrogated NMJ overgrowth and the increase in BMP signaling. A lipidomic analysis revealed that Acsl suppressed the levels of three lipid raft components in the brain, including mannosyl glucosylceramide (MacCer), phosphoethanolamine ceramide and ergosterol. The MacCer level was elevated in Acsl mutant NMJs and, along with sterol, promoted NMJ overgrowth, but was not associated with the increase in BMP signaling in the mutants. These findings suggest that Acsl inhibits NMJ growth by stimulating C16:1 fatty acyl production and concomitantly suppressing raft-associated lipid levels.

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“…These lipid species are considered to infl uence phototransduction events by allowing alteration of membrane topology upon rhodopsin photo-isomerization, while serving as quenchers of free radical-species formed by photon exposure (BoeszeBattaglia and Schimmel, 1997;Litman and Mitchell, 1996;McMahon and Kedzierski, 2010;Sanchez-Martin et al 2013). In contrast, Drosophila tissues lack medium and long chain PUFAs (Hammad et al 2011;Shen et al 2010), and as the current study shows, its rhabdomeres do not contain fatty acids over 18 carbons and are slightly enriched in saturated FA (Table 2); these features would reduce membrane fl uidity through higher PL compaction. Still, PL composition of rhabdomere membranes shows the highest levels of polyunsaturated fatty acids (C18:2 and C18:3), suggesting that in the absence of very long chain highly unsaturated fatty acids such as DHA, Drosophila uses C18 unsaturated fatty acids to overcome partially membrane compaction.…”

Section: Discussionmentioning

confidence: 99%

“…These technological improvements have allowed a dramatic refi nement in the resolution of the measurements of molecular components in spatially confi ned cellular regions, previously obscured by contamination from adjacent cellular compartments with which they were inevitably associated in the biological samples. Thus although there are good characterizations of the general lipid and fatty acid composition of Drosophila tissues (Carvalho et al 2012;Hammad et al 2011;Shen et al 2010), there is an evident lack of information regarding the fatty acids that make up the specific lipid species present in Drosophila photoreceptor rhabdomere membranes; this represents a serious handicap for the understanding of the mechanism underlying light transduction (recently reviewed in Raghu et al 2012). Although the phospholipid composition of these membranes has been characterized and the balance between phosphatidic acid and phosphatidylinositol species linked to both rhabdomere biogenesis (Raghu et al, 2006) and degeneration (García-Murillas et al, 2006), there are no data on the fatty acid composition of these tissues, which is crucial in the understanding of the mechanisms of activation of TRP channels and phototransduction accessory proteins embedded in this lipid-rich environment (see Raghu et al (2012) and references therein).…”

Section: Discussionmentioning

confidence: 99%

“…It is remarkable that a Drosophila rhabdomere membrane preparation suitable for biochemical studies such as lipidomics is not available. To date lipidomic characterizations Fatty acid composition of Drosophila photoreceptor light-sensitive microvilli of Drosophila fatty acids have been performed on entire fl ies or heads (Carvalho et al 2012;Hammad et al 2011;Shen et al 2010), while studies on Drosophila retinas have focused on the levels of general lipid components and have not determined the presence or abundance of specifi c fatty acids (Fujita et al 1987;Garcia-Murillas et al 2006;Raghu et al 2009). …”

Section: Introductionmentioning

confidence: 99%

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Fatty acid composition of Drosophila photoreceptor light-sensitive microvilli

et al. 2013

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Phototransduction, the mechanism underlying the electrical response to light in photoreceptor cells, has been thoroughly investigated in Drosophila melanogaster, an essential model in signal transduction research. These cells present a highly specialized photosensitive membrane consisting of thousands of microvilli forming a prominent structure termed a rhabdomere. These microvilli encompass the phototransduction proteins, most of which are transmembrane and exclusively rhabdomeric. Rhabdomere membrane lipids play a crucial role in the activation of the transient receptor potential ionic channels (TRP and TRPL) responsible for initiating the photoresponse. Despite its importance, rhabdomere lipid composition has not been established. We developed a novel preparation enriched in rhabdomere membranes to perform a thorough characterization of the lipidomics of Drosophila rhabdomeres. Isolated eyes (500) were homogenized and subjected to a diff erential centrifugation protocol that generates a fraction enriched in rhabdomere membrane. Lipids extracted from this preparation were identifi ed and quantifi ed by gas chromatography coupled to mass spectrometry. We found an abundance of low sterol esters (C16:0, C18:0), highly abundant and diverse triglycerides, free fatty acids, a moderate variety of mono and diacyglycerols (C:16:0, 18:0, C18:1) and abundant phospholipids (principally C18:2). This preparation opens a new avenue for investigating essential aspects of phototransduction.

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Drosophila lacks C20 and C22 PUFAs

Cited by 99 publications

References 14 publications

The Effects of Hempseed Meal Intake and Linoleic Acid on Drosophila Models of Neurodegenerative Diseases and Hypercholesterolemia

The Effects of Hempseed Meal Intake and Linoleic Acid on Drosophila Models of Neurodegenerative Diseases and Hypercholesterolemia

Acsl, the Drosophila ortholog of intellectual-disability-related ACSL4, inhibits synaptic growth by altered lipids

Fatty acid composition of Drosophila photoreceptor light-sensitive microvilli

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