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ADCY5 Gene Expression in Adipose Tissue Is Related to Obesity in Men and Mice

Genome wide association studies revealed an association of the single nucleotide polymorphism rs11708067 within the ADCY5 gene—encoding adenylate cyclase 5—with increased type 2 diabetes (T2D) risk and higher fasting glucose. However, it remains unclear whether the association between ADCY5 variants...

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Autores principales: Knigge, Anja, Klöting, Nora, Schön, Michael R., Dietrich, Arne, Fasshauer, Mathias, Gärtner, Daniel, Lohmann, Tobias, Dreßler, Miriam, Stumvoll, Michael, Kovacs, Peter, Blüher, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368112/
https://www.ncbi.nlm.nih.gov/pubmed/25793868
http://dx.doi.org/10.1371/journal.pone.0120742
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author Knigge, Anja
Klöting, Nora
Schön, Michael R.
Dietrich, Arne
Fasshauer, Mathias
Gärtner, Daniel
Lohmann, Tobias
Dreßler, Miriam
Stumvoll, Michael
Kovacs, Peter
Blüher, Matthias
author_facet Knigge, Anja
Klöting, Nora
Schön, Michael R.
Dietrich, Arne
Fasshauer, Mathias
Gärtner, Daniel
Lohmann, Tobias
Dreßler, Miriam
Stumvoll, Michael
Kovacs, Peter
Blüher, Matthias
author_sort Knigge, Anja
collection PubMed
description Genome wide association studies revealed an association of the single nucleotide polymorphism rs11708067 within the ADCY5 gene—encoding adenylate cyclase 5—with increased type 2 diabetes (T2D) risk and higher fasting glucose. However, it remains unclear whether the association between ADCY5 variants and glycemic traits may involve adipose tissue (AT) related mechanisms. We therefore tested the hypothesis that ADCY5 mRNA expression in human and mouse AT is related to obesity, fat distribution, T2D in humans and high fat diet (HFD) in mice. We measured ADCY5 mRNA expression in paired samples of visceral and subcutaneous adipose tissue from 244 individuals with a wide range of body weight and parameters of hyperglycemia, which have been genotyped for rs11708067. In addition, AT ADCY5 mRNA was assessed in C57BL/6NTac which underwent a 10 weeks standard chow (n = 6) or high fat diet (HFD, n = 6). In humans, visceral ADCY5 expression is significantly higher in obese compared to lean individuals. ADCY5 expression correlates with BMI, body fat mass, circulating leptin, fat distribution, waist and hip circumference, but not with fasting plasma glucose and HbA1c. Adcy5 expression in mouse AT is significantly higher after a HFD compared to chow (p<0.05). Importantly, rs11708067 is not associated with ADCY5 mRNA expression levels in either fat depot in any of the genetic models tested. Our results suggest that changes in AT ADCY5 expression are related to obesity and fat distribution, but not with impaired glucose metabolism and T2D. However, altered ADCY5 expression in AT does not seem to be the mechanism underlying the association between rs11708067 and increased T2D risk.
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spelling pubmed-43681122015-03-27 ADCY5 Gene Expression in Adipose Tissue Is Related to Obesity in Men and Mice Knigge, Anja Klöting, Nora Schön, Michael R. Dietrich, Arne Fasshauer, Mathias Gärtner, Daniel Lohmann, Tobias Dreßler, Miriam Stumvoll, Michael Kovacs, Peter Blüher, Matthias PLoS One Research Article Genome wide association studies revealed an association of the single nucleotide polymorphism rs11708067 within the ADCY5 gene—encoding adenylate cyclase 5—with increased type 2 diabetes (T2D) risk and higher fasting glucose. However, it remains unclear whether the association between ADCY5 variants and glycemic traits may involve adipose tissue (AT) related mechanisms. We therefore tested the hypothesis that ADCY5 mRNA expression in human and mouse AT is related to obesity, fat distribution, T2D in humans and high fat diet (HFD) in mice. We measured ADCY5 mRNA expression in paired samples of visceral and subcutaneous adipose tissue from 244 individuals with a wide range of body weight and parameters of hyperglycemia, which have been genotyped for rs11708067. In addition, AT ADCY5 mRNA was assessed in C57BL/6NTac which underwent a 10 weeks standard chow (n = 6) or high fat diet (HFD, n = 6). In humans, visceral ADCY5 expression is significantly higher in obese compared to lean individuals. ADCY5 expression correlates with BMI, body fat mass, circulating leptin, fat distribution, waist and hip circumference, but not with fasting plasma glucose and HbA1c. Adcy5 expression in mouse AT is significantly higher after a HFD compared to chow (p<0.05). Importantly, rs11708067 is not associated with ADCY5 mRNA expression levels in either fat depot in any of the genetic models tested. Our results suggest that changes in AT ADCY5 expression are related to obesity and fat distribution, but not with impaired glucose metabolism and T2D. However, altered ADCY5 expression in AT does not seem to be the mechanism underlying the association between rs11708067 and increased T2D risk. Public Library of Science 2015-03-20 /pmc/articles/PMC4368112/ /pubmed/25793868 http://dx.doi.org/10.1371/journal.pone.0120742 Text en © 2015 Knigge et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Knigge, Anja
Klöting, Nora
Schön, Michael R.
Dietrich, Arne
Fasshauer, Mathias
Gärtner, Daniel
Lohmann, Tobias
Dreßler, Miriam
Stumvoll, Michael
Kovacs, Peter
Blüher, Matthias
ADCY5 Gene Expression in Adipose Tissue Is Related to Obesity in Men and Mice
title ADCY5 Gene Expression in Adipose Tissue Is Related to Obesity in Men and Mice
title_full ADCY5 Gene Expression in Adipose Tissue Is Related to Obesity in Men and Mice
title_fullStr ADCY5 Gene Expression in Adipose Tissue Is Related to Obesity in Men and Mice
title_full_unstemmed ADCY5 Gene Expression in Adipose Tissue Is Related to Obesity in Men and Mice
title_short ADCY5 Gene Expression in Adipose Tissue Is Related to Obesity in Men and Mice
title_sort adcy5 gene expression in adipose tissue is related to obesity in men and mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368112/
https://www.ncbi.nlm.nih.gov/pubmed/25793868
http://dx.doi.org/10.1371/journal.pone.0120742
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