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Genetic dissection ...
Genetic dissection of serum vaspin highlights its causal role in lipid metabolism
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- Breitfeld, Jana (author)
- Leipzig University
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- Horn, Katrin (author)
- Leipzig University
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- Le Duc, Diana (author)
- University Hospital Leipzig,Max Planck Institute for Evolutionary Anthropology
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- Velluva, Akhil (author)
- Max Planck Institute for Evolutionary Anthropology,Leipzig University
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- Marzi, Carola (author)
- German Center for Diabetes Research,Helmholtz Zentrum München
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- Grallert, Harald (author)
- Helmholtz Zentrum München,German Center for Diabetes Research
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- Friedrich, Nele (author)
- German Centre for Cardiovascular Research,University Hospital Greifswald
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- Pietzner, Maik (author)
- German Centre for Cardiovascular Research,Berlin Institute of Health (BIH)
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- Völker, Uwe (author)
- University Hospital Greifswald,German Centre for Cardiovascular Research
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- Völzke, Henry (author)
- University Hospital Greifswald
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- Ahlqvist, Emma (author)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Aly, Dina Mansour (author)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Tuomi, Tiinamaija (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,University of Helsinki,Helsinki University Central Hospital
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- Baber, Ronny (author)
- Leipzig University
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- Kratzsch, Jürgen (author)
- Leipzig University
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- Thiery, Joachim (author)
- University of Kiel
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- Isermann, Berend (author)
- Leipzig University
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- Loeffler, Markus (author)
- Leipzig University
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- Klöting, Nora (author)
- University Hospital Leipzig
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- Blüher, Matthias (author)
- University Hospital Leipzig
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- Stumvoll, Michael (author)
- German Center for Diabetes Research,Helmholtz Zentrum München,Leipzig University
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- Heiker, John T. (author)
- University Hospital Leipzig
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- Tönjes, Anke (author)
- Leipzig University
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- Scholz, Markus (author)
- Leipzig University
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- Kovacs, Peter (author)
- Leipzig University
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Obesity. - 1930-7381. ; 31:11, s. 2862-2874
- Related links:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- Objective: 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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Obesity
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To the university's database
- By the author/editor
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Breitfeld, Jana
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Horn, Katrin
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Le Duc, Diana
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Velluva, Akhil
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Marzi, Carola
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Grallert, Harald
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show more...
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Friedrich, Nele
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Pietzner, Maik
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Völker, Uwe
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Völzke, Henry
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Ahlqvist, Emma
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Aly, Dina Mansou ...
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Tuomi, Tiinamaij ...
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Baber, Ronny
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Kratzsch, Jürgen
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Thiery, Joachim
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Isermann, Berend
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Loeffler, Markus
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Klöting, Nora
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Blüher, Matthias
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Stumvoll, Michae ...
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Heiker, John T.
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Tönjes, Anke
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Scholz, Markus
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Kovacs, Peter
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Obesity
- By the university
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Lund University