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  • 1
    Online Resource
    Online Resource
    Genetic dissection of serum vaspin highlights its causal role in lipid metabolism
    Wiley ; 2023
    In:  Obesity
    Details
    In: Obesity, Wiley
    Abstract: Vaspin (visceral adipose tissue derived serine protease inhibitor, SERPINA12 ) is associated with obesity‐related metabolic traits, but its causative role is still elusive. The role of genetics in serum vaspin variability to establish its causal relationship with metabolically relevant traits was investigated. Methods A meta‐analysis of genome‐wide association studies for serum vaspin from six independent cohorts (N = 7446) was conducted. Potential functional variants of vaspin were included in Mendelian randomization (MR) analyses to assess possible causal pathways between vaspin and homeostasis model assessment and lipid traits. To further validate the MR analyses, data from Genotype‐Tissue Expression (GTEx) were analyzed, db/db mice were treated with vaspin, and serum lipids were measured. Results A total of 468 genetic variants represented by five independent variants (rs7141073, rs1956709, rs4905216, rs61978267, rs73338689) within the vaspin locus were associated with serum vaspin (all p   〈  5×10 −8 , explained variance 16.8%). MR analyses revealed causal relationships between serum vaspin and triglycerides, low‐density lipoprotein, and total cholesterol. Gene expression correlation analyses suggested that genes, highly correlated with vaspin expression in adipose tissue, are enriched in lipid metabolic processes. Finally, in vivo vaspin treatment reduced serum triglycerides in obese db/db mice. Conclusions The data show that serum vaspin is strongly determined by genetic variants within vaspin , which further highlight vaspin's causal role in lipid metabolism.
    Type of Medium: Online Resource
    ISSN: 1930-7381 , 1930-739X
    URL: Article
    DOI: 10.1002/oby.23882
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2027211-X
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  • 2
    Online Resource
    Online Resource
    DNA methylation patterns reflect individual's lifestyle independent of obesity
    Wiley ; 2022
    In:  Clinical and Translational Medicine Vol. 12, No. 6 ( 2022-06)
    Details
    In: Clinical and Translational Medicine, Wiley, Vol. 12, No. 6 ( 2022-06)
    Abstract: Obesity is driven by modifiable lifestyle factors whose effects may be mediated by epigenetics. Therefore, we investigated lifestyle effects on blood DNA methylation in participants of the LIFE‐Adult study, a well‐characterised population‐based cohort from Germany. Research design and methods Lifestyle scores (LS) based on diet, physical activity, smoking and alcohol intake were calculated in 4107 participants of the LIFE‐Adult study. Fifty subjects with an extremely healthy lifestyle and 50 with an extremely unhealthy lifestyle (5th and 95th percentiles LS) were selected for genome‐wide DNA methylation analysis in blood samples employing Illumina Infinium® Methylation EPIC BeadChip system technology. Results Differences in DNA methylation patterns between body mass index groups ( 〈 25 vs. 〉 30 kg/m 2 ) were rather marginal compared to inter‐lifestyle differences (0 vs. 145 differentially methylated positions [DMPs]), which identified 4682 differentially methylated regions (DMRs; false discovery rate [FDR  〈 5%) annotated to 4426 unique genes. A DMR annotated to the glutamine‐fructose‐6‐phosphate transaminase 2 ( GFPT2 ) locus showed the strongest hypomethylation (∼6.9%), and one annotated to glutamate rich 1 ( ERICH1 ) showed the strongest hypermethylation (∼5.4%) in healthy compared to unhealthy lifestyle individuals. Intersection analysis showed that diet, physical activity, smoking and alcohol intake equally contributed to the observed differences, which affected, among others, pathways related to glutamatergic synapses (adj. p   〈  .01) and axon guidance (adj. p   〈  .05). We showed that methylation age correlates with chronological age and waist‐to‐hip ratio with lower DNA methylation age (DNAmAge) acceleration distances in participants with healthy lifestyles. Finally, two identified top DMPs for the alanyl aminopeptidase ( ANPEP ) locus also showed the strongest expression quantitative trait methylation in blood. Conclusions DNA methylation patterns help discriminate individuals with a healthy versus unhealthy lifestyle, which may mask subtle methylation differences derived from obesity.
    Type of Medium: Online Resource
    ISSN: 2001-1326 , 2001-1326
    URL: Issue
    URL: Article
    DOI: 10.1002/ctm2.v12.6
    DOI: 10.1002/ctm2.851
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2697013-2
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  • 3
    Online Resource
    Online Resource
    The role of rs2237781 within GRM8 in eating behavior
    Wiley ; 2013
    In:  Brain and Behavior Vol. 3, No. 5 ( 2013-09), p. 495-502
    Details
    In: Brain and Behavior, Wiley, Vol. 3, No. 5 ( 2013-09), p. 495-502
    Abstract: The glutamate receptor , metabotropic 8 gene ( GRM8 ) encodes a G‐protein‐coupled glutamate receptor and has been associated with smoking behavior and liability to alcoholism implying a role in addiction vulnerability. Data from animal studies suggest that GRM8 may be involved in the regulation of the neuropeptide Y and melanocortin pathways and might influence food intake and metabolism. This study aimed to investigate the effects of the genetic variant rs2237781 within GRM8 on human eating behavior. Methods: The initial analysis included 548 Sorbs from Germany who have been extensively phenotyped for metabolic traits and who completed the German version of the three‐factor eating questionnaire. In addition, we analyzed two independent sample sets comprising 293 subjects from another German cohort and 430 Old Order Amish individuals. Genetic associations with restraint, disinhibition, and hunger were assessed in an additive linear regression model. Results: Among the Sorbs the major G allele of rs2237781 was significantly associated with increased restraint scores in eating behavior ( P  =   1.9 × 10 −4 ; β  = +1.936). The German cohort and the Old Order Amish population revealed a trend in the same direction for restraint ( P  =   0.242; β  = +0.874; P  = 0.908; β  = +0.096; respectively). A meta‐analysis resulted in a combined P  =   3.1 × 10 −3 ( Z ‐score 2.948). Conclusion: Our data suggest that rs2237781 within GRM8 may influence human eating behavior factors probably via pathways involved in addictive behavior.
    Type of Medium: Online Resource
    ISSN: 2162-3279 , 2162-3279
    URL: Issue
    URL: Article
    DOI: 10.1002/brb3.2013.3.issue-5
    DOI: 10.1002/brb3.151
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 2623587-0
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  • 4
    Online Resource
    Online Resource
    Circulating Adipokine VASPIN Is Associated with Serum Lipid Profiles in Humans
    Wiley ; 2019
    In:  Lipids Vol. 54, No. 4 ( 2019-04), p. 203-210
    Details
    In: Lipids, Wiley, Vol. 54, No. 4 ( 2019-04), p. 203-210
    Abstract: VASPIN , visceral adipose tissue‐derived serpin, is an adipokine ameliorating insulin resistance in obesity. Here, we investigated the role of VASPIN and its genetic variants in lipid metabolism. We measured serum VASPIN concentrations by ELISA in 823 metabolically well‐characterized Caucasian subjects (Sorbs from Germany). Furthermore, we genotyped 30 representative single nucleotide polymorphisms (SNP) in two independent cohorts with metabolic phenotyping, the Sorbs ( N  = 823) and Leipzig ( N  = 919), and conducted genotype–phenotype association analyses. Circulating VASPIN strongly correlated with triacylglycerol levels (TAG; p  = 1.079 × 10 −11 ), and moderately with apolipoprotein A1 and low‐density lipoprotein cholesterol ( p  = 0.026). Genetic variants in VASPIN were nominally associated with cholesterol, high‐density and low‐density lipoprotein (HDL‐chol, LDL‐chol), lipoprotein A, and apolipoprotein B as well as with TAG and free fatty acids (all p   〈  0.05 adjusted for age, sex, and body mass index [BMI]). Mendelian randomization analysis using VASPIN SNP as an instrumental variable showed borderline influence of VASPIN on LDL‐chol levels ( p  = 0.05). Associations of VASPIN and its genetic variation with metabolic traits suggest a role of VASPIN in human lipid metabolism.
    Type of Medium: Online Resource
    ISSN: 0024-4201 , 1558-9307
    URL: Issue
    URL: Article
    DOI: 10.1002/lipd.2019.54.issue-4
    DOI: 10.1002/lipd.12139
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2030265-4
    SSG: 12
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