Regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase

Shi, Xun; Li, Juan; Zou, Xiaoju; Greggain, Joel; Rødkær, Steven Vestergaard; Færgeman, Nils J.; Liang, Bin; Watts, Jennifer L.

doi:10.1194/jlr.m039669

Cited by 136 publications

(142 citation statements)

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“…When SCD1 is defective the saturation of ER phospholipids increases, which favors the formation of very small LDs ( Figures 6A and 6I-6K). This phenotype has been consistently observed in Caenorhabditis elegans with defective SCD1 (Shi et al, 2013), or in adipose tissues wherein Seipin dysfunction impaired SCD1 activity (Boutet et al, 2009;Lounis et al, 2016).…”

Section: Discussionmentioning

confidence: 91%

ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation

et al. 2017

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SUMMARYCells convert excess energy into neutral lipids that are made in the endoplasmic reticulum (ER) bilayer. The lipids are then packaged into spherical or budded lipid droplets (LDs) covered by a phospholipid monolayer containing proteins. LDs play a key role in cellular energy metabolism and homeostasis. A key unanswered question in the life of LDs is how they bud off from the ER. Here, we tackle this question by studying the budding of artificial LDs from model membranes. We find that the bilayer phospholipid composition and surface tension are key parameters of LD budding. Phospholipids have differential LD budding aptitudes, and those inducing budding decrease the bilayer tension. We observe that decreasing tension favors the egress of neutral lipids from the bilayer and LD budding. In cells, budding conditions favor the formation of small LDs. Our discovery reveals the importance of altering ER physical chemistry for controlled cellular LD formation.

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Section: Discussionmentioning

confidence: 91%

ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation

et al. 2017

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“…Fatty acid supplementation was carried out by adding sodium oleic acid (OA) (NuChek Prep) at a final concentration of 0.2 mM to NGM media as we previously described (Shi et al 2013). Synchronized L1 worms were cultivated on NGM agar plates supplemented with OA.…”

Section: Lipid Extraction and Analysismentioning

confidence: 99%

“…Lipid extraction and analysis of young adult nematodes was determined as described previously (Watts and Browse 2006;Shi et al 2013). To determine the triacylglycerol (TAG) and phospholipids, lipid extraction, thin-layer chromatography (TLC), and gas chromatography (GC) were performed as described (Watts and Browse 2006;Shi et al 2013).…”

Section: Lipid Extraction and Analysismentioning

confidence: 99%

“…Quantification of the diameter of lipid droplets (LDs) was followed as described by Shi et al (2013). In brief, young adult worms were fixed and stained by Nile Red and photographed.…”

Section: Quantification Of Lipid Droplet Sizementioning

confidence: 99%

“…To determine the triacylglycerol (TAG) and phospholipids, lipid extraction, thin-layer chromatography (TLC), and gas chromatography (GC) were performed as described (Watts and Browse 2006;Shi et al 2013).…”

Section: Lipid Extraction and Analysismentioning

confidence: 99%

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Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans

Wang¹,

Jiang

et al. 2016

Genetics

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The trace element iron is crucial for living organisms, since it plays essential roles in numerous cellular functions. Systemic iron overload and the elevated level of ferritin, a ubiquitous intracellular protein that stores and releases iron to maintain the iron homeostasis in cells, has long been epidemiologically associated with obesity and obesity-related diseases. However, the underlying mechanisms of this association remain unclear. Here, using Caenorhabditis elegans, we show that iron overload induces the expression of sgk-1, encoding the serum and glucocorticoid-inducible kinase, to promote the level of ferritin and fat accumulation. Mutation of cyp-23A1, encoding a homolog of human cytochrome P450 CYP7B1 that is related to neonatal hemochromatosis, further enhances the elevated expression of ftn-1, sgk-1, and fat accumulation. sgk-1 positively regulates the expression of acs-20 and vit-2, genes encoding homologs of the mammalian FATP1/4 fatty acid transport proteins and yolk lipoproteins, respectively, to facilitate lipid uptake and translocation for storage under iron overload. This study reveals a completely novel pathway in which sgk-1 plays a central role to synergistically regulate iron and lipid homeostasis, offering not only experimental evidence supporting a previously unverified link between iron and obesity, but also novel insights into the pathogenesis of iron and obesity-related human metabolic diseases. KEYWORDS iron; serum and glucocorticoid inducible kinase SGK-1; lipid uptake; obesity; C. elegans D UE to its essential roles in numerous cellular functions across nearly all living organisms, including oxygen transport, electron transport, DNA synthesis, and enzyme catalysis, exploring how iron is stored and regulated has been a growing focus in numerous fields. Dietary iron is absorbed primarily by duodenal enterocytes via the divalent metal-ion transporter 1 (DMT1) after it is reduced at the apical membrane. Subsequently, it is either stored in ferritin, which dynamically regulates iron sequestration, storage, and release or it is transported from enterocytes into the blood stream via the basolateral transporter ferroportin (Fleming and Ponka 2012). Consequently, the total amount of iron in the body is determined by its intake and storage, which are all finely regulated by many factors and signaling pathways at various levels (Fleming and Ponka 2012;Hubler et al. 2015), many of which not entirely understood.Human epidemiology studies revealed that elevated levels of ferritin may be an indication of systemic iron overload (Cook et al. 1974;Zimmermann 2008) and are positively associated with obesity (Wenzel et al. 1962;Gillum 2001;Iwasaki et al. 2005) and obesity-related diseases such as diabetes, hypertension, dyslipidaemia, or nonalcoholic fatty liver disease (Jehn et al. 2004;Bozzini et al. 2005;Mascitelli et al. 2009;Dongiovanni et al. 2011;Kim et al. 2011; see Zafon et al. 2010 for review). Precisely why elevations in ferritin levels or systemic iron overload are associated w...

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Antioxidant and reducing lipid accumulation effects of rutin in Caenorhabditis elegans

2021

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In this study, the effect of rutin on fatty acid metabolism and antioxidant activity were evaluated. We found that the antioxidant capacity of rutin‐treated Caenorhabditis elegans was enhanced but the triglyceride content was significantly reduced. The reduction of fat accumulation by rutin was also confirmed by Oil Red O staining. RNA‐seq analysis indicated that rutin significantly regulated the expression of seven genes related to lipid metabolism in C. elegans. Among the seven genes, acox‐1.3, stdh‐3, and fat‐7 were associated with fatty acid metabolism. Rutin significantly reduced fat accumulation in both fat‐6 and fat‐7 mutant strains but did not affect the fat storage of fat‐6/fat‐7 double mutant, which indicated that the impact of rutin on fat storage depended on fat‐6 and fat‐7. These findings indicated that rutin reduced fat storage depending on the regulation of lipid metabolism‐related genes expression and thereby regulating the biosynthesis of the corresponding unsaturated fatty acid.

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Regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase

Cited by 136 publications

References 58 publications

ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation

ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation

Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans

Antioxidant and reducing lipid accumulation effects of rutin in Caenorhabditis elegans

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