Glucosylceramide synthase in the fat body controls energy metabolism in Drosophila

Kohyama-Koganeya, Ayako; Nabetani, Takuji; Miura, Masayuki; Hirabayashi, Yoshio

doi:10.1194/jlr.m014266

Cited by 41 publications

(36 citation statements)

References 25 publications

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“…We propose that the controlled expression of gGlcT1 is critical for lipid internalization in trophozoites because overexpression or knocking down of this enzyme affects ESV biogenesis and cyst viability. The observation that gGlcT1 regulates the overall lipid balance/homeostasis in Giardia was further supported by the report that GlcT1 overexpression influences several body fat storage genes in Drosophila (56) and also that the interactions between SL and other branches of the lipid metabolic pathways are essential for maintaining lipid homeostasis in mammalian cells (57,58).…”

Section: Discussionsupporting

confidence: 52%

Glucosylceramide Transferase Activity Is Critical for Encystation and Viable Cyst Production by an Intestinal Protozoan, Giardia lamblia

Mendez

Chatterjee

Duarte

et al. 2013

Journal of Biological Chemistry

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Background:The production of viable cysts by Giardia is essential for transmitting the infection via contaminated food and water. Results: Overexpression and knockdown of glucosylceramide transferase activity affect encystation, cyst viability, and overall lipid balance in Giardia. Conclusion: Regulated expression of glucosylceramide transferase is linked to encystation and cyst production. Significance: Glucosylceramide synthesis could be targeted for developing novel anti-giardial therapy.

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Section: Discussionsupporting

confidence: 52%

Glucosylceramide Transferase Activity Is Critical for Encystation and Viable Cyst Production by an Intestinal Protozoan, Giardia lamblia

Mendez

Chatterjee

Duarte

et al. 2013

Journal of Biological Chemistry

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“…In this context, it is worth mentioning that GlcT can also regulate TAG levels in Drosophila in an ATF2 dependent manner [17]. It will certainly be worth to determine whether or not this regulation might be mediated via changes in Schlank protein activity.…”

Section: Discussionmentioning

confidence: 99%

“…These observations suggest that besides having enzymatic function in ceramide synthesis, Schlank has a novel function of regulating the balance between lipogenesis and lipolysis in Drosophila [5]. Recent analysis of the Drosophila Glucosylceramide synthase (GlcT-1) showed that Glc-T1 in the fat body also controls fat metabolism [17]. Subsequent reports of mammalian CerS models support a role of CerS and their derived ceramide metabolites in lipid homeostasis [18,19].…”

mentioning

confidence: 98%

NuclearDrosophilaCerS Schlank regulates lipid homeostasis via the homeodomain, independent of the lag1p motif

et al. 2016

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Edited by Laszlo NagyDrosophila Ceramide Synthase (CerS) Schlank regulates both ceramide synthesis and fat metabolism. Schlank contains a catalytic lag1p motif and, like many CerS in other species, a homeodomain of unknown function. Here, we show that the Drosophila CerS Schlank is imported into the nucleus and requires two nuclear localization signals (NLSs) within its homeodomain and functional Importin-b import machinery. Expression of Schlank variants containing the homeodomain without functional lag1p motif rescued the fat metabolism phenotype of schlank mutants whereas a variant with a mutated NLS site did not rescue. Thus, the homeodomain of Schlank is involved in the regulation of lipid metabolism independent of the catalytic lag1p motif.Keywords: ceramide synthase; Drosophila; homeodomain; importin; lipid homeostasis; nuclear function Ceramides and sphingolipids are key intermediates in diverse cellular processes for growth, stress resistance, apoptosis, neurodegeneration, insulin function, and lipid homeostasis [1][2][3][4][5].In synthesis of ceramide, Ceramide Synthases (CerSs) acylate a sphingoid long-chain base (LCB) with a fatty acyl-CoA of distinct length to generate (dihydro) ceramide, the backbone of all complex sphAbbreviations aa, amino acid; ASAH1, acid ceramidase; ATF2, activating transcription factor 2; cDNA, complementary DNA; CerSs, ceramide synthases; dsRNA, double-stranded RNA; ER, endoplasmic reticulum; Gal4, galactose-responsive transcription factor; GFP, green fluorescent protein; GlcT-1, glucosylceramide synthase; H215D, change in a histidine at position 215 of schlank into glutamate; INM, inner nuclear membrane;

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“…Similarly to ceramide, glucosylceramide appears to also have effects unrelated to its impact on insulin. After observing and noting increased glucosylceramides in adipose of mammals and drosophila, Kohyama-Koganeya et al (123) questioned the role of glucosylceramides in regulating energy storage. They found that GCS overexpression increased lipid and carbohydrate storage in the drosophila fat body, essentially giving the flies a "pot belly."…”

Section: Glucosylated Ceramides In the Regulation Of Metabolismmentioning

confidence: 99%

Ceramides as modulators of cellular and whole-body metabolism

Bikman¹,

Summers²

2011

J. Clin. Invest.

362

297

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Nearly all stress stimuli (e.g., inflammatory cytokines, glucocorticoids, chemotherapeutics, etc.) induce sphingolipid synthesis, leading to the accumulation of ceramides and ceramide metabolites. While the role of these lipids in the regulation of cell growth and death has been studied extensively, recent studies suggest that a primary consequence of ceramide accumulation is an alteration in metabolism. In both cell-autonomous systems and complex organisms, ceramides modify intracellular signaling pathways to slow anabolism, ensuring that catabolism ensues. These ceramide actions have important implications for diseases associated with obesity, such as diabetes and cardiovascular disease. Conflict of interest:The authors have declared that no conflict of interest exists.Citation for this article:

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Glucosylceramide synthase in the fat body controls energy metabolism in Drosophila

Cited by 41 publications

References 25 publications

Glucosylceramide Transferase Activity Is Critical for Encystation and Viable Cyst Production by an Intestinal Protozoan, Giardia lamblia

Glucosylceramide Transferase Activity Is Critical for Encystation and Viable Cyst Production by an Intestinal Protozoan, Giardia lamblia

NuclearDrosophilaCerS Schlank regulates lipid homeostasis via the homeodomain, independent of the lag1p motif

Ceramides as modulators of cellular and whole-body metabolism

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