LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 5 of total 5

Search options

  1. Article ; Online: Systems genetics analysis of human body fat distribution genes identifies adipocyte processes.

    Reed, Jordan N / Huang, Jiansheng / Li, Yong / Ma, Lijiang / Banka, Dhanush / Wabitsch, Martin / Wang, Tianfang / Ding, Wen / Björkegren, Johan Lm / Civelek, Mete

    Life science alliance

    2024  Volume 7, Issue 7

    Abstract: Excess abdominal fat is a sexually dimorphic risk factor for cardio-metabolic disease and is approximated by the waist-to-hip ratio adjusted for body mass index ( ... ...

    Abstract Excess abdominal fat is a sexually dimorphic risk factor for cardio-metabolic disease and is approximated by the waist-to-hip ratio adjusted for body mass index (WHR
    MeSH term(s) Humans ; Adipocytes/metabolism ; Male ; Female ; Body Fat Distribution ; Adipogenesis/genetics ; Body Mass Index ; Adult ; Gene Regulatory Networks ; Middle Aged ; Bayes Theorem ; Waist-Hip Ratio ; Adipose Tissue/metabolism ; Wnt Signaling Pathway/genetics ; Gene Expression Regulation/genetics ; Systems Biology/methods
    Language English
    Publishing date 2024-05-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202402603
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article: Systems genetics analysis of human body fat distribution genes identifies Wnt signaling and mitochondrial activity in adipocytes.

    Reed, Jordan N / Huang, Jiansheng / Li, Yong / Ma, Lijiang / Banka, Dhanush / Wabitsch, Martin / Wang, Tianfang / Ding, Wen / Björkegren, Johan L M / Civelek, Mete

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Background: Excess fat in the abdomen is a sexually dimorphic risk factor for cardio-metabolic disease. The relative storage between abdominal and lower-body subcutaneous adipose tissue depots is approximated by the waist-to-hip ratio adjusted for body ... ...

    Abstract Background: Excess fat in the abdomen is a sexually dimorphic risk factor for cardio-metabolic disease. The relative storage between abdominal and lower-body subcutaneous adipose tissue depots is approximated by the waist-to-hip ratio adjusted for body mass index (WHRadjBMI). Genome-wide association studies (GWAS) identified 346 loci near 495 genes associated with WHRadjBMI. Most of these genes have unknown roles in fat distribution, but many are expressed and putatively act in adipose tissue. We aimed to identify novel sex- and depot-specific drivers of WHRadjBMI using a systems genetics approach.
    Methods: We used two independent cohorts of adipose tissue gene expression with 362 - 444 males and 147 - 219 females, primarily of European ancestry. We constructed sex- and depot- specific Bayesian networks to model the gene-gene interactions from 8,492 adipose tissue genes. Key driver analysis identified genes that, in silico and putatively in vitro, regulate many others, including the 495 WHRadjBMI GWAS genes. Key driver gene function was determined by perturbing their expression in human subcutaneous pre-adipocytes using lenti-virus or siRNA.
    Results: 51 - 119 key drivers in each network were replicated in both cohorts. We used single-cell expression data to select replicated key drivers expressed in adipocyte precursors and mature adipocytes, prioritized genes which have not been previously studied in adipose tissue, and used public human and mouse data to nominate 53 novel key driver genes (10 - 21 from each network) that may regulate fat distribution by altering adipocyte function. In other cell types, 23 of these genes are found in crucial adipocyte pathways: Wnt signaling or mitochondrial function. We selected seven genes whose expression is highly correlated with WHRadjBMI to further study their effects on adipogenesis/Wnt signaling (ANAPC2, PSME3, RSPO1, TYRO3) or mitochondrial function (C1QTNF3, MIGA1, PSME3, UBR1).Adipogenesis was inhibited in cells overexpressing ANAPC2 and RSPO1 compared to controls. RSPO1 results are consistent with a positive correlation between gene expression in the subcutaneous depot and WHRadjBMI, therefore lower relative storage in the subcutaneous depot. RSPO1 inhibited adipogenesis by increasing β-catenin activation and Wnt-related transcription, thus repressing PPARG and CEBPA. PSME3 overexpression led to more adipogenesis than controls. In differentiated adipocytes, MIGA1 and UBR1 downregulation led to mitochondrial dysfunction, with lower oxygen consumption than controls; MIGA1 knockdown also lowered UCP1 expression.
    Summary: ANAPC2, MIGA1, PSME3, RSPO1,
    Language English
    Publishing date 2023-09-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.06.556534
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Adipocyte-Specific Modulation of KLF14 Expression in Mice Leads to Sex-Dependent Impacts on Adiposity and Lipid Metabolism.

    Yang, Qianyi / Hinkle, Jameson / Reed, Jordan N / Aherrahrou, Redouane / Xu, Zhiwen / Harris, Thurl E / Stephenson, Erin J / Musunuru, Kiran / Keller, Susanna R / Civelek, Mete

    Diabetes

    2022  Volume 71, Issue 4, Page(s) 677–693

    Abstract: Genome-wide association studies identified single nucleotide polymorphisms on chromosome 7 upstream of KLF14 to be associated with metabolic syndrome traits and increased risk for type 2 diabetes (T2D). The associations were more significant in women ... ...

    Abstract Genome-wide association studies identified single nucleotide polymorphisms on chromosome 7 upstream of KLF14 to be associated with metabolic syndrome traits and increased risk for type 2 diabetes (T2D). The associations were more significant in women than in men. The risk allele carriers expressed lower levels of the transcription factor KLF14 in adipose tissues than nonrisk allele carriers. To investigate how adipocyte KLF14 regulates metabolic traits in a sex-dependent manner, we characterized high-fat diet-fed male and female mice with adipocyte-specific Klf14 deletion or overexpression. Klf14 deletion resulted in increased fat mass in female mice and decreased fat mass in male mice. Female Klf14-deficient mice had overall smaller adipocytes in subcutaneous fat depots but larger adipocytes in parametrial depots, indicating a shift in lipid storage from subcutaneous to visceral fat depots. They had reduced metabolic rates and increased respiratory exchange ratios consistent with increased use of carbohydrates as an energy source. Fasting- and isoproterenol-induced adipocyte lipolysis was defective in female Klf14-deficient mice, and concomitantly, adipocyte triglycerides lipase mRNA levels were downregulated. Female Klf14-deficient mice cleared blood triglyceride and nonesterified fatty acid less efficiently than wild-type. Finally, adipocyte-specific overexpression of Klf14 resulted in lower total body fat in female but not male mice. Taken together, consistent with human studies, adipocyte KLF14 deficiency in female but not in male mice causes increased adiposity and redistribution of lipid storage from subcutaneous to visceral adipose tissues. Increasing KLF14 abundance in adipocytes of females with obesity and T2D may provide a novel treatment option to alleviate metabolic abnormalities.
    MeSH term(s) Adipocytes/metabolism ; Adiposity/genetics ; Animals ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Female ; Genome-Wide Association Study ; Kruppel-Like Transcription Factors/genetics ; Kruppel-Like Transcription Factors/metabolism ; Lipid Metabolism/genetics ; Male ; Mice ; Obesity/genetics ; Obesity/metabolism ; Sex Factors
    Chemical Substances Klf14 protein, mouse ; Kruppel-Like Transcription Factors
    Language English
    Publishing date 2022-01-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db21-0674
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.175: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Genes in human obesity loci are causal obesity genes in C. elegans.

    Ke, Wenfan / Reed, Jordan N / Yang, Chenyu / Higgason, Noel / Rayyan, Leila / Wählby, Carolina / Carpenter, Anne E / Civelek, Mete / O'Rourke, Eyleen J

    PLoS genetics

    2021  Volume 17, Issue 9, Page(s) e1009736

    Abstract: Obesity and its associated metabolic syndrome are a leading cause of morbidity and mortality. Given the disease's heavy burden on patients and the healthcare system, there has been increased interest in identifying pharmacological targets for the ... ...

    Abstract Obesity and its associated metabolic syndrome are a leading cause of morbidity and mortality. Given the disease's heavy burden on patients and the healthcare system, there has been increased interest in identifying pharmacological targets for the treatment and prevention of obesity. Towards this end, genome-wide association studies (GWAS) have identified hundreds of human genetic variants associated with obesity. The next challenge is to experimentally define which of these variants are causally linked to obesity, and could therefore become targets for the treatment or prevention of obesity. Here we employ high-throughput in vivo RNAi screening to test for causality 293 C. elegans orthologs of human obesity-candidate genes reported in GWAS. We RNAi screened these 293 genes in C. elegans subject to two different feeding regimens: (1) regular diet, and (2) high-fructose diet, which we developed and present here as an invertebrate model of diet-induced obesity (DIO). We report 14 genes that promote obesity and 3 genes that prevent DIO when silenced in C. elegans. Further, we show that knock-down of the 3 DIO genes not only prevents excessive fat accumulation in primary and ectopic fat depots but also improves the health and extends the lifespan of C. elegans overconsuming fructose. Importantly, the direction of the association between expression variants in these loci and obesity in mice and humans matches the phenotypic outcome of the loss-of-function of the C. elegans ortholog genes, supporting the notion that some of these genes would be causally linked to obesity across phylogeny. Therefore, in addition to defining causality for several genes so far merely correlated with obesity, this study demonstrates the value of model systems compatible with in vivo high-throughput genetic screening to causally link GWAS gene candidates to human diseases.
    MeSH term(s) Animals ; Caenorhabditis elegans/genetics ; Dietary Carbohydrates/administration & dosage ; Fructose/administration & dosage ; Gene Expression ; Genetic Predisposition to Disease ; Homeostasis ; Humans ; Meta-Analysis as Topic ; Obesity/genetics ; Phenotype
    Chemical Substances Dietary Carbohydrates ; Fructose (30237-26-4)
    Language English
    Publishing date 2021-09-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1009736
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Development of a Broad-Spectrum Antimicrobial Combination for the Treatment of Staphylococcus aureus and Pseudomonas aeruginosa Corneal Infections.

    Chojnacki, Michaelle / Philbrick, Alesa / Wucher, Benjamin / Reed, Jordan N / Tomaras, Andrew / Dunman, Paul M / Wozniak, Rachel A F

    Antimicrobial agents and chemotherapy

    2018  Volume 63, Issue 1

    Abstract: Staphylococcus ... ...

    Abstract Staphylococcus aureus
    MeSH term(s) Animals ; Anti-Bacterial Agents/pharmacology ; Cornea/drug effects ; Cornea/microbiology ; Cornea/pathology ; Disease Models, Animal ; Drug Resistance, Multiple, Bacterial/drug effects ; Drug Synergism ; Drug Therapy, Combination ; Eye Infections, Bacterial/drug therapy ; Eye Infections, Bacterial/microbiology ; Eye Infections, Bacterial/pathology ; Female ; Humans ; Keratitis/drug therapy ; Keratitis/microbiology ; Keratitis/pathology ; Mice ; Mice, Inbred BALB C ; Moxifloxacin/pharmacology ; Ophthalmic Solutions/pharmacology ; Polymyxin B/pharmacology ; Pseudomonas Infections/drug therapy ; Pseudomonas Infections/microbiology ; Pseudomonas Infections/pathology ; Pseudomonas aeruginosa/drug effects ; Pseudomonas aeruginosa/growth & development ; Pseudomonas aeruginosa/pathogenicity ; Rifampin/pharmacology ; Staphylococcal Infections/drug therapy ; Staphylococcal Infections/microbiology ; Staphylococcal Infections/pathology ; Staphylococcus aureus/drug effects ; Staphylococcus aureus/growth & development ; Staphylococcus aureus/pathogenicity ; Treatment Outcome ; Trimethoprim/pharmacology
    Chemical Substances Anti-Bacterial Agents ; Ophthalmic Solutions ; Trimethoprim (AN164J8Y0X) ; Polymyxin B (J2VZ07J96K) ; Moxifloxacin (U188XYD42P) ; Rifampin (VJT6J7R4TR)
    Language English
    Publishing date 2018-12-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.01929-18
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 809: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Einzelsignatur: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top