title: ADCY5 gene expression in adipose tissue is related to obesity in men and mice.
abstract: 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.
authors: Department of Medicine, Dermatology und Neurology, Department of Endocrinology und Nephrology, University of Leipzig, Leipzig, Germany.
authors: Anja
authors: A
authors: Knigge
authors: Department of Medicine, Dermatology und Neurology, Department of Endocrinology und Nephrology, University of Leipzig, Leipzig, Germany; Junior Research Group 2 "Animal models of obesity", Integriertes Forschungs- und Behandlungszentrum (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany.
authors: Nora
authors: N
authors: Klöting
authors: Clinic of Visceral Surgery, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany.
authors: Michael R
authors: MR
authors: Schön
authors: Department of Surgery, University of Leipzig, Leipzig, Germany.
authors: Arne
authors: A
authors: Dietrich
authors: Department of Medicine, Dermatology und Neurology, Department of Endocrinology und Nephrology, University of Leipzig, Leipzig, Germany.
authors: Mathias
authors: M
authors: Fasshauer
authors: Clinic of Visceral Surgery, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany.
authors: Daniel
authors: D
authors: Gärtner
authors: Municipal Clinic Dresden-Neustadt, Dresden, Germany.
authors: Tobias
authors: T
authors: Lohmann
authors: Municipal Clinic Dresden-Neustadt, Dresden, Germany.
authors: Miriam
authors: M
authors: Dreßler
authors: Department of Medicine, Dermatology und Neurology, Department of Endocrinology und Nephrology, University of Leipzig, Leipzig, Germany.
authors: Michael
authors: M
authors: Stumvoll
authors: Integriertes Forschungs- und Behandlungszentrum (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany.
authors: Peter
authors: P
authors: Kovacs
authors: Department of Medicine, Dermatology und Neurology, Department of Endocrinology und Nephrology, University of Leipzig, Leipzig, Germany.
authors: Matthias
authors: M
authors: Blüher
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D000273:Adipose Tissue / Q000201:enzymology*; D050154:Adiposity; D000818:Animals; D059305:Diet, High-Fat; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019655:Quantitative Trait, Heritable; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V; D005947:Glucose