Identification of sphingolipid metabolites that induce obesity via misregulation of appetite, caloric intake and fat storage in Drosophila.

Abstract:

:Obesity is defined by excessive lipid accumulation. However, the active mechanistic roles that lipids play in its progression are not understood. Accumulation of ceramide, the metabolic hub of sphingolipid metabolism, has been associated with metabolic syndrome and obesity in humans and model systems. Here, we use Drosophila genetic manipulations to cause accumulation or depletion of ceramide and sphingosine-1-phosphate (S1P) intermediates. Sphingolipidomic profiles were characterized across mutants for various sphingolipid metabolic genes using liquid chromatography electrospray ionization tandem mass spectroscopy. Biochemical assays and microscopy were used to assess classic hallmarks of obesity including elevated fat stores, increased body weight, resistance to starvation induced death, increased adiposity, and fat cell hypertrophy. Multiple behavioral assays were used to assess appetite, caloric intake, meal size and meal frequency. Additionally, we utilized DNA microarrays to profile differential gene expression between these flies, which mapped to changes in lipid metabolic pathways. Our results show that accumulation of ceramides is sufficient to induce obesity phenotypes by two distinct mechanisms: 1) Dihydroceramide (C14:0) and ceramide diene (C14:2) accumulation lowered fat store mobilization by reducing adipokinetic hormone- producing cell functionality and 2) Modulating the S1P: ceramide (C14:1) ratio suppressed postprandial satiety via the hindgut-specific neuropeptide like receptor dNepYr, resulting in caloric intake-dependent obesity.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Walls SM Jr,Attle SJ,Brulte GB,Walls ML,Finley KD,Chatfield DA,Herr DR,Harris GL

doi

10.1371/journal.pgen.1003970

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

e1003970

issue

12

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-13-01940

journal_volume

9

pub_type

杂志文章
  • Yeast pol4 promotes tel1-regulated chromosomal translocations.

    abstract::DNA double-strand breaks (DSBs) are one of the most dangerous DNA lesions, since their erroneous repair by nonhomologous end-joining (NHEJ) can generate harmful chromosomal rearrangements. PolX DNA polymerases are well suited to extend DSB ends that cannot be directly ligated due to their particular ability to bind to...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003656

    authors: Ruiz JF,Pardo B,Sastre-Moreno G,Aguilera A,Blanco L

    更新日期:2013-01-01 00:00:00

  • Role of the single-stranded DNA-binding protein SsbB in pneumococcal transformation: maintenance of a reservoir for genetic plasticity.

    abstract::Bacteria encode a single-stranded DNA (ssDNA) binding protein (SSB) crucial for genome maintenance. In Bacillus subtilis and Streptococcus pneumoniae, an alternative SSB, SsbB, is expressed uniquely during competence for genetic transformation, but its precise role has been disappointingly obscure. Here, we report our...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002156

    authors: Attaiech L,Olivier A,Mortier-Barrière I,Soulet AL,Granadel C,Martin B,Polard P,Claverys JP

    更新日期:2011-06-01 00:00:00

  • RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases.

    abstract::Mitochondrial translation defects can be due to mutations affecting mitochondrial- or nuclear-encoded components. The number of known nuclear genes involved in mitochondrial translation has significantly increased in the past years. RCC1L (WBSCR16), a putative GDP/GTP exchange factor, has recently been described to in...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008923

    authors: Reyes A,Favia P,Vidoni S,Petruzzella V,Zeviani M

    更新日期:2020-07-31 00:00:00

  • Effects of aneuploidy on genome structure, expression, and interphase organization in Arabidopsis thaliana.

    abstract::Aneuploidy refers to losses and/or gains of individual chromosomes from the normal chromosome set. The resulting gene dosage imbalance has a noticeable affect on the phenotype, as illustrated by aneuploid syndromes, including Down syndrome in humans, and by human solid tumor cells, which are highly aneuploid. Although...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000226

    authors: Huettel B,Kreil DP,Matzke M,Matzke AJ

    更新日期:2008-10-01 00:00:00

  • CorE from Myxococcus xanthus is a copper-dependent RNA polymerase sigma factor.

    abstract::The dual toxicity/essentiality of copper forces cells to maintain a tightly regulated homeostasis for this metal in all living organisms, from bacteria to humans. Consequently, many genes have previously been reported to participate in copper detoxification in bacteria. Myxococcus xanthus, a prokaryote, encodes many p...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002106

    authors: Gómez-Santos N,Pérez J,Sánchez-Sutil MC,Moraleda-Muñoz A,Muñoz-Dorado J

    更新日期:2011-06-01 00:00:00

  • Time dependent genetic analysis links field and controlled environment phenotypes in the model C4 grass Setaria.

    abstract::Vertical growth of plants is a dynamic process that is influenced by genetic and environmental factors and has a pronounced effect on overall plant architecture and biomass composition. We have performed six controlled growth trials of an interspecific Setaria italica x Setaria viridis recombinant inbred line populati...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006841

    authors: Feldman MJ,Paul RE,Banan D,Barrett JF,Sebastian J,Yee MC,Jiang H,Lipka AE,Brutnell TP,Dinneny JR,Leakey ADB,Baxter I

    更新日期:2017-06-23 00:00:00

  • A comprehensive genetic characterization of bacterial motility.

    abstract::We have developed a powerful experimental framework that combines competitive selection and microarray-based genetic footprinting to comprehensively reveal the genetic basis of bacterial behaviors. Application of this method to Escherichia coli motility identifies 95% of the known flagellar and chemotaxis genes, and r...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0030154

    authors: Girgis HS,Liu Y,Ryu WS,Tavazoie S

    更新日期:2007-09-01 00:00:00

  • STK-12 acts as a transcriptional brake to control the expression of cellulase-encoding genes in Neurospora crassa.

    abstract::Cellulolytic fungi have evolved a complex regulatory network to maintain the precise balance of nutrients required for growth and hydrolytic enzyme production. When fungi are exposed to cellulose, the transcript levels of cellulase genes rapidly increase and then decline. However, the mechanisms underlying this bell-s...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008510

    authors: Lin L,Wang S,Li X,He Q,Benz JP,Tian C

    更新日期:2019-11-25 00:00:00

  • A point mutation decouples the lipid transfer activities of microsomal triglyceride transfer protein.

    abstract::Apolipoprotein B-containing lipoproteins (B-lps) are essential for the transport of hydrophobic dietary and endogenous lipids through the circulation in vertebrates. Zebrafish embryos produce large numbers of B-lps in the yolk syncytial layer (YSL) to move lipids from yolk to growing tissues. Disruptions in B-lp produ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008941

    authors: Wilson MH,Rajan S,Danoff A,White RJ,Hensley MR,Quinlivan VH,Recacha R,Thierer JH,Tan FJ,Busch-Nentwich EM,Ruddock L,Hussain MM,Farber SA

    更新日期:2020-08-06 00:00:00

  • MORC2B is essential for meiotic progression and fertility.

    abstract::The microrchidia (MORC) family proteins are chromatin-remodelling factors and function in diverse biological processes such as DNA damage response and transposon silencing. Here, we report that mouse Morc2b encodes a functional germ cell-specific member of the MORC protein family. Morc2b arose specifically in the rode...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007175

    authors: Shi B,Xue J,Zhou J,Kasowitz SD,Zhang Y,Liang G,Guan Y,Shi Q,Liu M,Sha J,Huang X,Wang PJ

    更新日期:2018-01-12 00:00:00

  • Prp4 Kinase Grants the License to Splice: Control of Weak Splice Sites during Spliceosome Activation.

    abstract::The genome of the fission yeast Schizosaccharomyces pombe encodes 17 kinases that are essential for cell growth. These include the cell-cycle regulator Cdc2, as well as several kinases that coordinate cell growth, polarity, and morphogenesis during the cell cycle. In this study, we further characterized another of the...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005768

    authors: Eckert D,Andrée N,Razanau A,Zock-Emmenthal S,Lützelberger M,Plath S,Schmidt H,Guerra-Moreno A,Cozzuto L,Ayté J,Käufer NF

    更新日期:2016-01-05 00:00:00

  • Fuzzy tandem repeats containing p53 response elements may define species-specific p53 target genes.

    abstract::Evolutionary forces that shape regulatory networks remain poorly understood. In mammals, the Rb pathway is a classic example of species-specific gene regulation, as a germline mutation in one Rb allele promotes retinoblastoma in humans, but not in mice. Here we show that p53 transactivates the Retinoblastoma-like 2 (R...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002731

    authors: Simeonova I,Lejour V,Bardot B,Bouarich-Bourimi R,Morin A,Fang M,Charbonnier L,Toledo F

    更新日期:2012-06-01 00:00:00

  • Differential paralog divergence modulates genome evolution across yeast species.

    abstract::Evolutionary outcomes depend not only on the selective forces acting upon a species, but also on the genetic background. However, large timescales and uncertain historical selection pressures can make it difficult to discern such important background differences between species. Experimental evolution is one tool to c...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006585

    authors: Sanchez MR,Miller AW,Liachko I,Sunshine AB,Lynch B,Huang M,Alcantara E,DeSevo CG,Pai DA,Tucker CM,Hoang ML,Dunham MJ

    更新日期:2017-02-14 00:00:00

  • A combinatorial amino acid code for RNA recognition by pentatricopeptide repeat proteins.

    abstract::The pentatricopeptide repeat (PPR) is a helical repeat motif found in an exceptionally large family of RNA-binding proteins that functions in mitochondrial and chloroplast gene expression. PPR proteins harbor between 2 and 30 repeats and typically bind single-stranded RNA in a sequence-specific fashion. However, the b...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002910

    authors: Barkan A,Rojas M,Fujii S,Yap A,Chong YS,Bond CS,Small I

    更新日期:2012-01-01 00:00:00

  • Intronic PAH gene mutations cause a splicing defect by a novel mechanism involving U1snRNP binding downstream of the 5' splice site.

    abstract::Phenylketonuria (PKU), one of the most common inherited diseases of amino acid metabolism, is caused by mutations in the phenylalanine hydroxylase (PAH) gene. Recently, PAH exon 11 was identified as a vulnerable exon due to a weak 3' splice site, with different exonic mutations affecting exon 11 splicing through disru...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007360

    authors: Martínez-Pizarro A,Dembic M,Pérez B,Andresen BS,Desviat LR

    更新日期:2018-04-23 00:00:00

  • Allele frequency matching between SNPs reveals an excess of linkage disequilibrium in genic regions of the human genome.

    abstract::Significant interest has emerged in mapping genetic susceptibility for complex traits through whole-genome association studies. These studies rely on the extent of association, i.e., linkage disequilibrium (LD), between single nucleotide polymorphisms (SNPs) across the human genome. LD describes the nonrandom associat...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0020142

    authors: Eberle MA,Rieder MJ,Kruglyak L,Nickerson DA

    更新日期:2006-09-08 00:00:00

  • PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance.

    abstract::Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal and cerebrovascular arteries. FMD is often an underdiagnosed cause of hypertension and stroke, has higher prevalence in females (~80%) but its pathophysiology is unclear. We an...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006367

    authors: Kiando SR,Tucker NR,Castro-Vega LJ,Katz A,D'Escamard V,Tréard C,Fraher D,Albuisson J,Kadian-Dodov D,Ye Z,Austin E,Yang ML,Hunker K,Barlassina C,Cusi D,Galan P,Empana JP,Jouven X,Gimenez-Roqueplo AP,Bruneval P,Hyun

    更新日期:2016-10-28 00:00:00

  • Curly Encodes Dual Oxidase, Which Acts with Heme Peroxidase Curly Su to Shape the Adult Drosophila Wing.

    abstract::Curly, described almost a century ago, is one of the most frequently used markers in Drosophila genetics. Despite this the molecular identity of Curly has remained obscure. Here we show that Curly mutations arise in the gene dual oxidase (duox), which encodes a reactive oxygen species (ROS) generating NADPH oxidase. U...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005625

    authors: Hurd TR,Liang FX,Lehmann R

    更新日期:2015-11-20 00:00:00

  • The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus.

    abstract::Efficient adaptation to iron starvation is an essential virulence determinant of the most common human mold pathogen, Aspergillus fumigatus. Here, we demonstrate that the cytosolic monothiol glutaredoxin GrxD plays an essential role in iron sensing in this fungus. Our studies revealed that (i) GrxD is essential for gr...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008379

    authors: Misslinger M,Scheven MT,Hortschansky P,López-Berges MS,Heiss K,Beckmann N,Heigl T,Hermann M,Krüger T,Kniemeyer O,Brakhage AA,Haas H

    更新日期:2019-09-16 00:00:00

  • Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose.

    abstract::During the adaptive evolution of a particular trait, some selectively fixed mutations may be directly causative and others may be purely compensatory. The relative contribution of these two classes of mutation to adaptive phenotypic evolution depends on the form and prevalence of mutational pleiotropy. To investigate ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007331

    authors: Natarajan C,Jendroszek A,Kumar A,Weber RE,Tame JRH,Fago A,Storz JF

    更新日期:2018-04-02 00:00:00

  • The transposon-like Correia elements encode numerous strong promoters and provide a potential new mechanism for phase variation in the meningococcus.

    abstract::Neisseria meningitidis is the primary causative agent of bacterial meningitis. The genome is rich in repetitive DNA and almost 2% is occupied by a diminutive transposon called the Correia element. Here we report a bioinformatic analysis defining eight subtypes of the element with four distinct types of ends. Transcrip...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001277

    authors: Siddique A,Buisine N,Chalmers R

    更新日期:2011-01-20 00:00:00

  • Loss of catalytically inactive lipid phosphatase myotubularin-related protein 12 impairs myotubularin stability and promotes centronuclear myopathy in zebrafish.

    abstract::X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by mutations of the myotubularin gene, MTM1. Myotubularin belongs to a large family of conserved lipid phosphatases that include both catalytically active and inactive myotubularin-related proteins (i.e., "MTMRs"). Biochemically, catalytically inacti...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003583

    authors: Gupta VA,Hnia K,Smith LL,Gundry SR,McIntire JE,Shimazu J,Bass JR,Talbot EA,Amoasii L,Goldman NE,Laporte J,Beggs AH

    更新日期:2013-06-01 00:00:00

  • Cardiomyocyte Regulation of Systemic Lipid Metabolism by the Apolipoprotein B-Containing Lipoproteins in Drosophila.

    abstract::The heart has emerged as an important organ in the regulation of systemic lipid homeostasis; however, the underlying mechanism remains poorly understood. Here, we show that Drosophila cardiomyocytes regulate systemic lipid metabolism by producing apolipoprotein B-containing lipoproteins (apoB-lipoproteins), essential ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006555

    authors: Lee S,Bao H,Ishikawa Z,Wang W,Lim HY

    更新日期:2017-01-17 00:00:00

  • Differential role of cytosolic Hsp70s in longevity assurance and protein quality control.

    abstract::70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70's in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and acc...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008951

    authors: Andersson R,Eisele-Bürger AM,Hanzén S,Vielfort K,Öling D,Eisele F,Johansson G,Gustafsson T,Kvint K,Nyström T

    更新日期:2021-01-11 00:00:00

  • The Thermoanaerobacter glycobiome reveals mechanisms of pentose and hexose co-utilization in bacteria.

    abstract::Thermoanaerobic bacteria are of interest in cellulosic-biofuel production, due to their simultaneous pentose and hexose utilization (co-utilization) and thermophilic nature. In this study, we experimentally reconstructed the structure and dynamics of the first genome-wide carbon utilization network of thermoanaerobes....

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002318

    authors: Lin L,Song H,Tu Q,Qin Y,Zhou A,Liu W,He Z,Zhou J,Xu J

    更新日期:2011-10-01 00:00:00

  • Correction: Protein Poly(ADP-ribosyl)ation Regulates Arabidopsis Immune Gene Expression and Defense Responses.

    abstract::[This corrects the article DOI: 10.1371/journal.pgen.1004936.]. ...

    journal_title:PLoS genetics

    pub_type: 已发布勘误

    doi:10.1371/journal.pgen.1005294

    authors: Feng B,Liu C,de Oliveira MV,Intorne AC,Li B,Babilonia K,de Souza Filho GA,Shan L,He P

    更新日期:2016-09-09 00:00:00

  • A Genome-wide hybrid incompatibility landscape between Caenorhabditis briggsae and C. nigoni.

    abstract::Systematic characterization of ẖybrid incompatibility (HI) between related species remains the key to understanding speciation. The genetic basis of HI has been intensively studied in Drosophila species, but remains largely unknown in other species, including nematodes, which is mainly due to the lack of a sister spec...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004993

    authors: Bi Y,Ren X,Yan C,Shao J,Xie D,Zhao Z

    更新日期:2015-02-18 00:00:00

  • Genomic inversions and GOLGA core duplicons underlie disease instability at the 15q25 locus.

    abstract::Human chromosome 15q25 is involved in several disease-associated structural rearrangements, including microdeletions and chromosomal markers with inverted duplications. Using comparative fluorescence in situ hybridization, strand-sequencing, single-molecule, real-time sequencing and Bionano optical mapping analyses, w...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008075

    authors: Maggiolini FAM,Cantsilieris S,D'Addabbo P,Manganelli M,Coe BP,Dumont BL,Sanders AD,Pang AWC,Vollger MR,Palumbo O,Palumbo P,Accadia M,Carella M,Eichler EE,Antonacci F

    更新日期:2019-03-27 00:00:00

  • Broad-specificity mRNA-rRNA complementarity in efficient protein translation.

    abstract::Studies of synthetic, well-defined biomolecular systems can elucidate inherent capabilities that may be difficult to uncover in a native biological context. Here, we used a minimal, reconstituted translation system from Escherichia coli to identify efficient ribosome binding sites (RBSs) in an unbiased, high-throughpu...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002598

    authors: Barendt PA,Shah NA,Barendt GA,Sarkar CA

    更新日期:2012-01-01 00:00:00

  • Cell-type specific features of circular RNA expression.

    abstract::Thousands of loci in the human and mouse genomes give rise to circular RNA transcripts; at many of these loci, the predominant RNA isoform is a circle. Using an improved computational approach for circular RNA identification, we found widespread circular RNA expression in Drosophila melanogaster and estimate that in h...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003777

    authors: Salzman J,Chen RE,Olsen MN,Wang PL,Brown PO

    更新日期:2013-01-01 00:00:00