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Tenomodulin Is Highly Expressed in Adipose Tissue, Increased in Obesity, and Down-Regulated during Diet-Induced Weight Loss

Sahlgrenska Center for Cardiovascular and Metabolic Research (A.S., M.O., M.J., A.G., J.A., P.J., K.S., B.O., B.C., L.S., P.-A.S., L.M.S.C.), Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at Gothenburg University, 41345 Gothenburg, Sweden; Diabetes and Metabolism Unit (P.G.M.), Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital Coventry and Warwickshire, Coventry CV2 2DX, United Kingdom; Faculty of Pharmaceutical Sciences (S.Y.), Josai International University, 285-8555 Chiba, Japan; Section of Genomic Medicine (J.A., A.W., P.F.), Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom; Centre National de la Recherche Scientifique-8090, Institute of Biology (P.F.), Pasteur Institute, 59019 Lille, France; and Department of Discovery Medicine (B.C.), AstraZeneca R&D, SE-431 83 Mölndal, Sweden

Address all correspondence and requests for reprints to: Dr. Per-Arne Svensson, Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at Gothenburg University, Vita Stråket 15, 413 45 Gothenburg, Sweden. E-mail: per-arne.svensson{at}medic.gu.se.

Context: Tenomodulin (TNMD), a putative angiogenesis inhibitor, is expressed in hypovascular connective tissues. Global gene expression scans show that the TNMD gene also is expressed in human adipose tissue and that its expression is regulated in response to weight reduction; however, more detailed information is lacking.

Objective: The aim of this study was to investigate TNMD tissue distribution and TNMD gene expression in human adipose tissue in relation to obesity and metabolic disease.

Design, Patients, and Interventions: TNMD gene expression, tissue distribution, and TNMD gene expression in adipose tissue from different depots, from lean and obese subjects, and during diet-induced weight reduction were analyzed by DNA microarray and real-time PCR.

Main Outcome Measure: We primarily measured TNMD gene expression.

Results: The TNMD gene was predominantly expressed in sc adipose tissue. TNMD gene expression was higher in sc than omental adipose tissue both in lean (P = 0.002) and obese subjects (P = 0.014). In both women and men, TNMD gene expression was significantly higher in the obese subjects compared to the lean subjects (P = 1.1 x 10^–26 and P = 0.010, respectively). In a multiple linear regression analysis, BMI was a significant independent predictor of TNMD gene expression. TNMD gene expression was down-regulated during diet-induced weight loss, with a 65% decrease after 18 wk of diet (P < 0.0001).

Conclusions: We conclude that human adipose tissue TNMD gene expression is highly affected by obesity, adipose tissue location, and weight loss, indicating that TNMD may play a role in adipose tissue function.