Lipid droplet-based storage fat metabolism in Drosophila

Kühnlein, Ronald P.

doi:10.1194/jlr.r024299

Cited by 127 publications

(87 citation statements)

References 63 publications

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“…The Drosophila genome encodes a single atlastin gene ( atl /CG6668) (Lee et al, 2008; Orso et al, 2009). We focused our analysis on the fat body, the major organ of fat storage in flies (Kühnlein, 2012). Atl was depleted by expressing an UAS-RNAi construct under control of the fat-body-specific Gal4 driver CgGal4 (Asha et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

A Conserved Role for Atlastin GTPases in Regulating Lipid Droplet Size

et al. 2013

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SUMMARY Lipid droplets (LDs) are the major fat storage organelles in eukaryotic cells, but how their size is regulated is unknown. Using genetic screens in C. elegans for LD morphology defects in intestinal cells, we found that mutations in atlastin, a GTPase required for homotypic fusion of endoplasmic reticulum (ER) membranes, cause not only ER morphology defects, but also a reduction in LD size. Similar results were obtained after depletion of atlastin or expression of a dominant-negative mutant, whereas overexpression of atlastin had the opposite effect. Atlastin depletion in Drosophila fat bodies also reduced LD size and decreased triglycerides in whole animals, sensitizing them to starvation. In mammalian cells, co-overexpression of atlastin-1 and REEP1, a paralog of the ER tubule-shaping protein DP1/REEP5, generates large LDs. The effect of atlastin-1 on LD size correlates with its activity to promote membrane fusion in vitro. Our results indicate that atlastin-mediated fusion of ER membranes is important for LD size regulation.

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Section: Resultsmentioning

confidence: 99%

A Conserved Role for Atlastin GTPases in Regulating Lipid Droplet Size

et al. 2013

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“…Despite having many conserved aspects of lipid storage and metabolic syndrome (Baker and Thummel, 2007; Kuhnlein, 2012), fruit flies do not synthesize long chain PUFAs (Shen et al, 2010). An important task will be to identify the lipid signaling molecules that are synthesized in D. melanogaster from 18-carbon fatty acids.…”

Section: Discussionmentioning

confidence: 99%

Polyunsaturated fatty acid derived signaling in reproduction and development: Insights from Caenorhabditis elegans and Drosophila melanogaster

Vrablik

Watts

2013

Molecular Reproduction Devel

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SUMMARY Polyunsaturated fatty acids (PUFAs) exhibit a diverse range of critical functions in biological systems. PUFAs modulate the biophysical properties of membranes and, along with their derivatives, the eicosanoids and endocannabinoids, form a wide array potent lipid signaling molecules. Much of our early understanding of PUFAs and PUFA-derived signaling stems from work in mammals; however, technological advances have made comprehensive lipid analysis possible in small genetic models such as Caenorhabditis elegans and Drosophila melanogaster. These models have a number of advantages, such as simple anatomy and genome-wide genetic screening techniques, which can broaden our understanding of fatty-acid-derived signaling in biological systems. Here we review what is known about PUFAs, eicosanoids, and endocannabinoids in the development and reproduction of C. elegans and D. melanogaster. Fatty acid signaling appears to be fundamental for multicellular organisms, and simple invertebrates often employ functionally similar pathways. In particular, studies in C. elegans and Drosophila are providing insight into the roles of PUFAs and PUFA-derived signaling in early developmental processes, such as meiosis, fertilization, and early embryonic cleavage.

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“…The genetic and metabolic complexity and gene redundancy in higher organisms complicates dissection of the fundamental genetic relationships involved in these diseases. However, the components and regulatory pathways of core metabolic pathways are generally highly conserved, making genetically simpler invertebrate models, such as Drosophila , well suited for such studies (Baker and Thummel, 2007; Botstein et al, 1997; Broughton et al, 2005; Diop and Bodmer, 2012; Kuehnlein, 2012; Noyes et al, 1995). Drosophila is unique in that it is the only invertebrate model organism with a beating heart for which suitable genetic tools and assays are available to study heart function (Bier and Bodmer, 2004; Ocorr et al, 2007; Wessells et al, 2004; Wolf et al, 2006; Ocorr et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

PGC-1/Spargel Counteracts High-Fat-Diet-Induced Obesity and Cardiac Lipotoxicity Downstream of TOR and Brummer ATGL Lipase

Diop¹,

Bisharat-Kernizan²,

Birse³

et al. 2015

Cell Reports

111

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SUMMARY Obesity and metabolic syndrome are associated with an increased risk for lipotoxic cardiomyopathy, which is strongly correlated with excessive accumulation of lipids in the heart. Obesity- and type 2 diabetes-related disorders have been linked to altered expression of the transcriptional cofactor PGC-1α, which regulates the expression of genes involved in energy metabolism. Using Drosophila, we identify PGC-1/spargel (PGC-1/srl) as a key antagonist of high-fat diet (HFD)-induced lipotoxic cardiomyopathy. We find that HFD-induced lipid accumulation and cardiac dysfunction are mimicked by reduced PGC-1/srl function and reversed by PGC-1/srl overexpression. Moreover, HFD feeding lowers PGC-1/srl expression by elevating TOR signaling and inhibiting expression of the Drosophila adipocyte triglyceride lipase (ATGL, Brummer), both of which function as upstream modulators of PGC-1/srl. The lipogenic transcription factor SREBP also contributes to HFD-induced cardiac lipotoxicity, likely in parallel with PGC-1/srl. These results suggest a regulatory network of key metabolic genes that modulates lipotoxic heart dysfunction.

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Lipid droplet-based storage fat metabolism in Drosophila

Cited by 127 publications

References 63 publications

A Conserved Role for Atlastin GTPases in Regulating Lipid Droplet Size

A Conserved Role for Atlastin GTPases in Regulating Lipid Droplet Size

Polyunsaturated fatty acid derived signaling in reproduction and development: Insights from Caenorhabditis elegans and Drosophila melanogaster

PGC-1/Spargel Counteracts High-Fat-Diet-Induced Obesity and Cardiac Lipotoxicity Downstream of TOR and Brummer ATGL Lipase

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