Genetic dissection of serum vaspin highlights its causal role in lipid metabolism

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Fältnamn	Indikatorer	Metadata
000		05205naa a2200565 4500
001		oai:lup.lub.lu.se:36833027-71b0-4660-aa61-c66be3b331f5
003		SwePub
008		231115s2023 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/36833027-71b0-4660-aa61-c66be3b331f52 URI
024	7	a https://doi.org/10.1002/oby.238822 DOI
040		a (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Breitfeld, Janau Leipzig University4 aut
245	1 0	a Genetic dissection of serum vaspin highlights its causal role in lipid metabolism
264	1	c 2023
520		a 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
700	1	a Horn, Katrinu Leipzig University4 aut
700	1	a Le Duc, Dianau University Hospital Leipzig,Max Planck Institute for Evolutionary Anthropology4 aut
700	1	a Velluva, Akhilu Max Planck Institute for Evolutionary Anthropology,Leipzig University4 aut
700	1	a Marzi, Carolau German Center for Diabetes Research,Helmholtz Zentrum München4 aut
700	1	a Grallert, Haraldu Helmholtz Zentrum München,German Center for Diabetes Research4 aut
700	1	a Friedrich, Neleu German Centre for Cardiovascular Research,University Hospital Greifswald4 aut
700	1	a Pietzner, Maiku German Centre for Cardiovascular Research,Berlin Institute of Health (BIH)4 aut
700	1	a Völker, Uweu University Hospital Greifswald,German Centre for Cardiovascular Research4 aut
700	1	a Völzke, Henryu University Hospital Greifswald4 aut
700	1	a Ahlqvist, Emmau Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups4 aut0 (Swepub:lu)infl-eah
700	1	a Aly, Dina Mansouru Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups4 aut0 (Swepub:lu)di3053ma
700	1	a Tuomi, Tiinamaijau Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,University of Helsinki,Helsinki University Central Hospital4 aut0 (Swepub:lu)ti8736tu
700	1	a Baber, Ronnyu Leipzig University4 aut
700	1	a Kratzsch, Jürgenu Leipzig University4 aut
700	1	a Thiery, Joachimu University of Kiel4 aut
700	1	a Isermann, Berendu Leipzig University4 aut
700	1	a Loeffler, Markusu Leipzig University4 aut
700	1	a Klöting, Norau University Hospital Leipzig4 aut
700	1	a Blüher, Matthiasu University Hospital Leipzig4 aut
700	1	a Stumvoll, Michaelu German Center for Diabetes Research,Helmholtz Zentrum München,Leipzig University4 aut
700	1	a Heiker, John T.u University Hospital Leipzig4 aut
700	1	a Tönjes, Ankeu Leipzig University4 aut
700	1	a Scholz, Markusu Leipzig University4 aut
700	1	a Kovacs, Peteru Leipzig University4 aut
710	2	a Leipzig Universityb University Hospital Leipzig4 org
773	0	t Obesityg 31:11, s. 2862-2874q 31:11<2862-2874x 1930-7381
856	4	u http://dx.doi.org/10.1002/oby.23882x freey FULLTEXT
856	4 8	u https://lup.lub.lu.se/record/36833027-71b0-4660-aa61-c66be3b331f5
856	4 8	u https://doi.org/10.1002/oby.23882

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