Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans

Zhang, Yuru; Zou, Xiaoju; Ding, Yi-Hong; Wang, Haizhen; Wu, Xiaoyun; Liang, Bin

doi:10.1186/1471-2164-14-164

Cited by 99 publications

(82 citation statements)

References 90 publications

(78 reference statements)

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“…The C. elegans genome contains 22 genes known to encode acyl-CoA synthetase/fatty acid transporter (Zhang et al 2013), of which ACS-20 is required for incorporation of exogenous very long chain fatty acids into sphingomyelin (Kage-Nakadai et al 2010). While ACS-22 may functionally overlap with ACS-20 (Kage-Nakadai et al 2010), we found that only ACS-20 is required for the increased fat accumulation under iron overload, suggesting that ACS-20, like SGK-1, regulates lipid hemostasis under iron overload.…”

Section: Discussionmentioning

confidence: 99%

“…Generally, dietary lipids are taken up by cells by lipid transporters. The C. elegans genome contains a number of genes with homology to known lipid transporters that may display similar or distinct functions (Zhang et al 2013). We tested several strains with mutations in putative lipid transporter genes including the acs-20(tm3232) strain, which carries a deletion in the acs-20 gene that encodes an ortholog of mammalian fatty acid transport proteins FATP1/4 (Kage-Nakadai et al 2010) (www.wormbase.org).…”

Section: The Fatty Acid Transporter Acs-20 Is Required For Ironinducementioning

confidence: 99%

“…The performance of RNAi by feeding was followed as we described previously (Zhang et al 2013). Worms were collected at 60 hr, at young adult stage, and GFP fluorescence was visualized under a fluorescence microscope (BX53, Olympus).…”

Section: Supplementation Of Facmentioning

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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Section: Discussionmentioning

confidence: 99%

Section: The Fatty Acid Transporter Acs-20 Is Required For Ironinducementioning

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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“…C. elegans stores fat in intestinal and hypodermal LDs (Hellerer et al 2007). Both mutant analysis and RNA interference (RNAi) screens in C. elegans have revealed evolutionarily conserved genes linked to LD size (Zhang et al 2013). Most of these genes encode proteins that participate in lipogenesis, ß-oxidation, phospholipid synthesis and binding, and the intracellular transport of fatty acids.…”

Section: Introductionmentioning

confidence: 99%

“…During the last decade, several genes involved in the synthesis, storage, and utilization of lipids have been identified in Caenorhabditis elegans and shown to be highly conserved (Zhang et al 2013). C. elegans stores fat in intestinal and hypodermal LDs (Hellerer et al 2007).…”

Section: Introductionmentioning

confidence: 99%

S-Adenosyl methionine synthetase 1 limits fat storage in Caenorhabditis elegans

Ehmke¹,

Luthe

Schnabel

et al. 2014

Genes Nutr

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Cytosolic lipid droplets are versatile, evolutionarily conserved organelles that are important for the storage and utilization of lipids in almost all cell types. To obtain insight into the physiological importance of lipid droplet size, we isolated and characterized a new S-adenosyl methionine synthetase 1 (SAMS-1)-deficient Caenorhabditis elegans mutant, which have enlarged lipid droplets throughout its life cycle. We found that the sams-1 mutant showed a markedly reduced body size and progeny number; impaired synthesis of phosphatidylcholine, a major membrane phospholipid; and elevated expression of key lipogenic genes, such as dgat-2, resulting in the accumulation of triacylglyceride in fewer, but larger, lipid droplets. The sams-1 mutant store more than 50 % (wild type: 10 %) of its intestinal fat in large lipid droplets, C10 lm 3 in size. In response to starvation, SAMS-1 deficiency causes reduced depletion of a subset of lipid droplets located in the anterior intestine. Given the importance of liberation of fatty acids from lipid droplets, we propose that the physiological function of SAMS-1, a highly conserved enzyme involved in one-carbon metabolism, is the limitation of fat storage to ensure proper growth and reproduction.

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C. elegansACAT regulates lipolysis and its related lifespan in fasting through modulation of the genes in lipolysis and insulin/IGF‐1 signaling

et al. 2020

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Overly active acyl-coenzyme A: cholesterol acyltransferases (ACATs) are known to contribute to the development of atherosclerosis, cancer cell proliferation and de novo lipogenesis. However, the role of ACAT in systemic lipid metabolism and its consequence of aging is unknown. Using avasimibe, a clinically proven ACAT inhibitor, and mboa-1 mutant strain, a homologous to mammalian ACAT, herein, we found that Ava treatment and mboa-1 mutant exhibited a decreased fat accumulation during feeding and increased lipolysis with extended lifespan of C. elegans during fasting. Our study highlights the essential role of ACAT inhibitor and mboa-1 in fat mobilization and the survival of C. elegans in fasting through the modulation of the genes involved in lipolysis and insulin/IGF-1 signaling.

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Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans

Cited by 99 publications

References 90 publications

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

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

S-Adenosyl methionine synthetase 1 limits fat storage in Caenorhabditis elegans

C. elegansACAT regulates lipolysis and its related lifespan in fasting through modulation of the genes in lipolysis and insulin/IGF‐1 signaling

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