ADCY5 gene expression in adipose tissue is related to obesity in men and mice.
ADCY5 gene expression in adipose tissue is related to obesity in men and mice.
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DOI：
10.1371/journal.pone.0120742
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Blüher M
中科院分区：
文献类型：
--
作者：
Knigge A;Klöting N;Schön MR;Dietrich A;Fasshauer M;Gärtner D;Lohmann T;Dreßler M;Stumvoll M;Kovacs P;Blüher M
全基因组关联研究显示，ADCY 5基因编码腺苷酸环化酶5-内的单核苷酸多态性rs 11708067与2型糖尿病（T2 D）风险增加和空腹血糖升高相关。然而，目前尚不清楚ADCY 5变异体和血糖性状之间的关联是否可能涉及脂肪组织（AT）相关机制。因此，我们测试了人类和小鼠AT中ADCY 5 mRNA表达与肥胖、脂肪分布、人类T2 D和小鼠高脂饮食（HFD）相关的假设。我们测量了ADCY 5 mRNA的表达配对样本的内脏和皮下脂肪组织从244个人与广泛的体重和高血糖症的参数，这已被基因分型为rs 11708067。此外，在经历10周标准食物（n = 6）或高脂肪饮食（HFD，n = 6）的C57 BL/6 NTac中评估AT ADCY 5 mRNA。在人类中，与瘦个体相比，肥胖者的内脏ADCY 5表达显著较高。ADCY 5表达与BMI、体脂量、循环瘦素、脂肪分布、腰围和臀围相关，但与空腹血糖和HbA 1c无关。与食物相比，HFD后小鼠AT中的Adcy 5表达显著更高（p<0.05）。重要的是，在任何测试的遗传模型中，rs 11708067与任一脂肪库中的ADCY 5 mRNA表达水平无关。我们的研究结果表明，ATADCY 5表达的变化与肥胖和脂肪分布有关，但与糖代谢受损和T2 D无关。然而，AT中ADCY 5表达的改变似乎不是rs 11708067与T2 D风险增加之间相关性的机制。
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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影响因子：
3.7
作者：
Windholz J;Kovacs P;Tönjes A;Dittrich K;Blüher S;Kiess W;Stumvoll M;Körner A
通讯作者：
Körner A
影响因子：
8.3
作者：
Ortiz-Capisano, M. Cecilia;Ortiz, Pablo A.;Beierwaltes, William H.
通讯作者：
Beierwaltes, William H.
DOI：
10.1152/ajpheart.00050.2009
发表时间：
2009-11-01
影响因子：
4.8
作者：
Hu, Che-Lin;Chandra, Rachna;Vatner, Dorothy E.
通讯作者：
Vatner, Dorothy E.
影响因子：
29
作者：
Kloeting, Nora;Graham, Timothy E.;Kahn, Barbara B.
通讯作者：
Kahn, Barbara B.
影响因子：
9
作者：
Du, W. W.;Yang, W.;Fang, L.;Xuan, J.;Li, H.;Khorshidi, A.;Gupta, S.;Li, X.;Yang, B. B.
通讯作者：
Yang, B. B.