Different mechanisms for selective transport of fatty acids using a single class of lipoprotein in Drosophila

Matsuo, Naoya; Nagao, Kazunori; Suito, Takuto; Juni, Naoto; Kato, Utako; Hara, Yuji; Umeda, Masato

doi:10.1194/jlr.m090779

Cited by 28 publications

(33 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S9); however, further studies are required to elucidate the mechanisms involved at the molecular level. We recently observed an accumulation of PUFA-containing phospholipids in the CNS of D. melanogaster 74 . PUFA-containing phospholipids are transported to the CNS through the receptor-mediated endocytosis of lipophorin 74 .…”

Section: Discussionmentioning

confidence: 96%

“…We recently observed an accumulation of PUFA-containing phospholipids in the CNS of D. melanogaster 74 . PUFA-containing phospholipids are transported to the CNS through the receptor-mediated endocytosis of lipophorin 74 . Accordingly, we detected remarkably high expression levels of lipophorin receptors LpR1 and LpR2 in the CNS.…”

Section: Discussionmentioning

confidence: 96%

“…LC-MS/MS analyses were performed using a high-performance liquid chromatography system LC-30AD (Shimadzu, Kyoto, Japan) coupled to a triple quadrupole mass spectrometer LC-MS-8040 (Shimadzu, Kyoto, Japan) that was equipped with an electrospray source as described previously 5,74 . The extracted phospholipids were separated using a Kinetex C8 column (2.6 μm, 2.1 × 150 mm) (Phenomenex, USA) with mobile phases comprising 10 mM ammonium formate in water (mobile phase A) and 10 mM ammonium formate in 2-propanol/acetonitrile/water (45/45/10) (mobile phase B).…”

Section: Establishment Of Uas-fat-2 and Uas-desat1 Transgenic Drosophmentioning

confidence: 99%

See 2 more Smart Citations

Functional expression of Δ12 fatty acid desaturase modulates thermoregulatory behaviour in Drosophila

Suito

Nagao

Takeuchi

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

polyunsaturated fatty acids (pUfAs) play crucial roles in adaptation to cold environments in a wide variety of animals and plants. However, the mechanisms by which PUFAs affect thermoregulatory behaviour remain elusive. Thus, we investigated the roles of PUFAs in thermoregulatory behaviour of Drosophila melanogaster. To this end, we generated transgenic flies expressing Caenorhabditis elegans Δ12 fatty acid desaturase (FAT-2), which converts mono-unsaturated fatty acids to PUFAs such as linoleic acid [C18:2 (n-6)] and linolenic acid [C18:3 (n-3)]. Neuron-specific expression of FAT-2 using the GAL4/UAS expression system led to increased contents of C18:2 (n-6)-containing phospholipids in central nerve system (CNS) and caused significant decreases in preferred temperature of third instar larvae. In genetic screening and calcium imaging analyses of thermoreceptor-expressing neurons, we demonstrated that ectopic expression of FAT-2 in TRPA1-expressing neurons led to decreases in preferred temperature by modulating neuronal activity. We conclude that functional expression of FAT-2 in a subset of neurons changes the thermoregulatory behaviour of D. melanogaster, likely by modulating quantities of PUFA-containing phospholipids in neuronal cell membranes. Polyunsaturated fatty acids (PUFAs) contain multiple double bonds in their hydrocarbon chains and, as bioactive lipids, regulate various animal physiological functions, such as those relating to immunity, reproduction and energy metabolism 1,2. PUFAs have also been implicated in thermal adaptation, particularly cold adaptation, because the cis double bonds in PUFAs create the "kinks" in hydrocarbon chain structures that reduce the packing of phospholipids, thus increasing membrane fluidity at low temperatures 3,4. For instance, ectothermic fish that live in low temperatures have high PUFA contents in phospholipids 5,6 , facilitating membrane fluidity 7 and modulating the activities of membrane proteins, such as Na +-K + ATPase 8 , in cold environments. Most organisms produce mono-unsaturated fatty acids from saturated fatty acids through the actions of Δ9 fatty acid desaturases 9-13. In mammals, PUFAs such as arachidonic acid [C20:4 (n-6)] and eicosapentaenoic acid [C20:5 (n-3)] are produced from linoleic acid [C18:2 (n-6)] and α-linolenic acid [C18:3 (n-3)], respectively, by Δ5 and Δ6 fatty acid desaturases. In contrast, Δ12 fatty acid desaturases that convert oleic acid [C18:1 (n-9)] to C18:2 (n-6), such as those in nematode Caenorhabditis elegans 14 , American cockroach 15 and cricket 16 , are found in few animals. Therefore, most animals have to obtain PUFAs, such as C18:2 (n-6) and C18:3 (n-3), from their diet. In bacteria 17 , protozoa 18 , algae 19,20 and plants 21,22 , Δ12 fatty acid desaturase can be reportedly induced following exposures to low temperatures. Hence, its biosynthetic product C18:2 (n-6) is thought to play crucial roles in low-temperature acclimation. C. elegans synthesises PUFAs using seven desaturases (FAT-1, FAT-2, FAT-3, FAT-4, FAT-5, FAT-6, ...

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Establishment Of Uas-fat-2 and Uas-desat1 Transgenic Drosophmentioning

confidence: 99%

See 1 more Smart Citation

Functional expression of Δ12 fatty acid desaturase modulates thermoregulatory behaviour in Drosophila

Suito

Nagao

Takeuchi

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…These data suggest that modulation of genes regulating both ceramide synthesis and degradation, specifically in the heart as well as the periphery, affect cardiac structure and function. Hemolymph-mediated transport of cardiotoxic sphingolipid metabolites between the fat body and heart might underlie these processes, although the effects of sphingosine Δ4 desaturase activity and its effects on general lipid metabolism are also likely to be major contributing factors (Matsuo et al, 2019). Interestingly, cardiac-specific ifc KD confers a restricted phenotype.…”

Section: Discussionmentioning

confidence: 99%

Systemic and heart autonomous effects of sphingosine Δ-4 desaturase deficiency in lipotoxic cardiac pathophysiology

Walls

Chatfield

Ocorr

et al. 2020

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Lipotoxic cardiomyopathy (LCM) is characterized by cardiac steatosis, including the accumulation of fatty acids, triglycerides and ceramides. Model systems have shown the inhibition of ceramide biosynthesis to antagonize obesity and improve insulin sensitivity. Sphingosine Δ4 desaturase (encoded by ifc in Drosophila melanogaster) enzymatically converts dihydroceramide into ceramide. Here, we examine ifc mutants to study the effects of desaturase deficiency on cardiac function in Drosophila. Interestingly, ifc mutants exhibited classic hallmarks of LCM: cardiac chamber dilation, contractile defects and loss of fractional shortening. This outcome was phenocopied in global ifc RNAi-mediated knockdown flies. Surprisingly, cardiac-specific ifc knockdown flies exhibited cardiac chamber restriction with no contractile defects, suggesting heart autonomous and systemic roles for ifc activity in cardiac function. Next, we demonstrated that ifc mutants exhibit suppressed Sphingosine kinase 1 (Sk1) expression. Ectopic overexpression of Sk1 was sufficient to prevent cardiac chamber dilation and loss of fractional shortening in ifc mutants. Partial rescue was also observed with cardiac- and fat-body-specific Sk1 overexpression. Finally, we showed that cardiac-specific expression of Drosophila inhibitor of apoptosis (dIAP) also prevented cardiac dysfunction in ifc mutants, suggesting a role for caspase activity in the observed cardiac pathology. Collectively, we show that spatial regulation of sphingosine Δ4 desaturase activity differentially affects cardiac function in heart autonomous and systemic mechanisms through tissue interplay.

show abstract

“…Moghadam, Holmstrup, Manenti, and Loeschcke () reported substantial proportions of 18:2 ( n ‐6) (24%) and 18:3 ( n ‐3) (9%) in D. melanogaster in flies reared on standard oatmeal‐agar‐sugar‐yeast medium, but again, no C20 PUFAs. As just seen in lepidopteran cell lines, three cell lines established from D. melanogaster , S2, BG2‐c6, and BG3‐c2 cells included AA, at 0.4%, 2.1%, and 3.8% of total fatty acids, respectively (Matsuo et al, ). We infer that D. melanogaster maintains at least catalytic levels of AA in tissue PLs.…”

mentioning

confidence: 99%

Why most insects have very low proportions of C20 polyunsaturated fatty acids: The oxidative stress hypothesis

Stanley

Kim

2019

Arch Insect Biochem Physiol

View full text Add to dashboard Cite

show abstract

Different mechanisms for selective transport of fatty acids using a single class of lipoprotein in Drosophila

Cited by 28 publications

References 65 publications

Functional expression of Δ12 fatty acid desaturase modulates thermoregulatory behaviour in Drosophila

Functional expression of Δ12 fatty acid desaturase modulates thermoregulatory behaviour in Drosophila

Systemic and heart autonomous effects of sphingosine Δ-4 desaturase deficiency in lipotoxic cardiac pathophysiology

Why most insects have very low proportions of C20 polyunsaturated fatty acids: The oxidative stress hypothesis

Contact Info

Product

Resources

About