Submitted on June 17, 2008
Revised on February 9, 2009
Accepted on February 10, 2009
RANTES RELEASE BY HUMAN ADIPOSE TISSUE IN VIVO AND EVIDENCE FOR DEPOT SPECIFIC DIFFERENCES
Rana Madani1, Kalypso Karastergiou1, Nicola Ogston2, Nazar Miheisi1, Rahul Bhome1, Nora Haloob1, Gary Tan3, Fredrik Karpe4, James Malone-Lee5, Marjan Jahangiri6, Majid Hashemi1, and Vidya Mohamed-Ali7*
1 University College London
2 Centre for Clinical Pharmacology, Department of Medicine, University College London, United Kingdom
3 University of Oxford
4 King Gustaf V Research Institute
5 Whittington Hospital, University College London
6 St George's University Hospital
7 University College London Medical School
* To whom correspondence should be addressed. E-mail: rmhavma{at}ucl.ac.uk.
Obesity is associated with elevated inflammatory signals from various adipose tissue depots. This study aimed to evaluate release of RANTES (Regulated upon Activation Normal T-cell Expressed and Secreted), by human adipose tissue in vivo and ex vivo, in reference to Monocyte Chemoattractant Protein-1 (MCP-1) and interleukin-6 (IL-6) release. Arteriovenous differences of RANTES, MCP-1 and IL-6 were studied in vivo across the abdominal subcutaneous adipose in healthy Caucasian subjects with a wide range of adiposity. Systemic levels and ex vivo RANTES release were studied in abdominal subcutaneous, gastric fat pad and omental adipose tissue from morbidly obese bariatric surgery patients, and in thoracic subcutaneous and epicardial adipose tissue from cardiac surgery patients, without coronary artery disease. Arteriovenous studies confirmed in vivo RANTES and IL-6 release in adipose tissue of lean and obese subjects, and that of MCP-1 in obesity. However, in vivo release of MCP-1 and RANTES, but not IL-6, was lower than circulating levels. Ex vivo release of RANTES was greater from the gastric fat pad compared to omental (p=0.01) and subcutaneous (p=0.001). Epicardial adipose tissue released less RANTES than thoracic subcutaneous in lean (p=0.04), but not in obese subjects. Indices of obesity correlated with epicardial RANTES but not with systemic RANTES or its release from other depots. In conclusion RANTES is released by human subcutaneous adipose tissue in vivo, and in varying amounts by other depots ex vivo. While it appears unlikely that the adipose organ contributes significantly to circulating levels, local implications of this chemokine deserve further investigation.
