RANTES release by human adipose tissue in vivo and evidence for depot-specific differences

Obesity is associated with elevated inflammatory signals from various adipose tissue depots. This study aimed to evaluate release of regulated on activation, normal T cell expressed and secreted (RANTES) 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 tissue 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 release 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 with omental (P = 0.01) and subcutaneous (P = 0.001) tissue. Epicardial adipose tissue released less RANTES than thoracic subcutaneous adipose tissue in lean (P = 0.04) but not obese subjects. Indexes 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.

[1]  E. Maury,et al.  Adipokines oversecreted by omental adipose tissue in human obesity. , 2007, American journal of physiology. Endocrinology and metabolism.

[2]  Julia K Mader,et al.  Adipose tissue, inflammation and cardiovascular disease. , 2010, Revista da Associacao Medica Brasileira.

[3]  Y. Matsuzawa,et al.  Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. , 1987, Metabolism: clinical and experimental.

[4]  G. Fielding,et al.  Laparoscopic adjustable gastric banding: surgical technique. , 2003, Journal of laparoendoscopic & advanced surgical techniques. Part A.

[5]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[6]  J S Yudkin,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor-�, in Vivo* , 2022 .

[7]  M. Dorf,et al.  RANTES-mediated Chemokine Transcription in Astrocytes Involves Activation and Translocation of p90 Ribosomal S6 Protein Kinase (RSK)* , 2002, The Journal of Biological Chemistry.

[8]  H. Sacks,et al.  Human epicardial adipose tissue: a review. , 2007, American heart journal.

[9]  S. O’Rahilly,et al.  The perils of portliness: causes and consequences of visceral adiposity. , 2000, Diabetes.

[10]  M. Skopkova,et al.  Protein Array Reveals Differentially Expressed Proteins in Subcutaneous Adipose Tissue in Obesity , 2007, Obesity.

[11]  S. Coppack,et al.  Adipose tissue as an endocrine and paracrine organ , 1998, International Journal of Obesity.

[12]  R. Holle,et al.  Association of systemic chemokine concentrations with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). , 2005, Diabetes.

[13]  S. Coppack,et al.  Metabolic characteristics of human adipose tissue in vivo. , 1989, Clinical science.

[14]  F. Terry.  Human obesity. , 1987, Annals of the New York Academy of Sciences.

[15]  P. Jansson,et al.  Adipose tissue metabolism in humans determined by vein catheterization and microdialysis techniques. , 1994, The American journal of physiology.

[16]  F. Mach,et al.  Antagonism of RANTES Receptors Reduces Atherosclerotic Plaque Formation in Mice , 2004, Circulation research.

[17]  J. H. Lee,et al.  Association of serum RANTES concentrations with established cardiovascular risk markers in middle-aged subjects. , 2009, International journal of cardiology.

[18]  Philipp E. Scherer,et al.  Visceral Fat Adipokine Secretion Is Associated With Systemic Inflammation in Obese Humans , 2007, Diabetes.

[19]  Liying Ma,et al.  Negative role of cAMP‐dependent protein kinase A in RANTES‐mediated transcription of proinflammatory mediators through Raf , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  Leif E. Peterson,et al.  T-Cell Accumulation and Regulated on Activation, Normal T Cell Expressed and Secreted Upregulation in Adipose Tissue in Obesity , 2007, Circulation.

[21]  Christian Weber,et al.  Ccr5 But Not Ccr1 Deficiency Reduces Development of Diet-Induced Atherosclerosis in Mice , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[22]  B. Ludvik,et al.  CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity. , 2008, The Journal of clinical endocrinology and metabolism.

[23]  C. Pond,et al.  Adipose tissue in the mammalian heart and pericardium: structure, foetal development and biochemical properties. , 1989, Comparative biochemistry and physiology. B, Comparative biochemistry.

[24]  A. Kissebah,et al.  Relationship of anthropometric measurements of body fat distribution to metabolic profile in premenopausal women. , 2009, Acta medica Scandinavica. Supplementum.

[25]  C. Pond,et al.  Site-specific properties of pericardial and epicardial adipose tissue: the effects of insulin and high-fat feeding on lipogenesis and the incorporation of fatty acids in vitro. , 1990, International journal of obesity.