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. 2009 Jun;296(6):E1262-8.
doi: 10.1152/ajpendo.90511.2008. Epub 2009 Feb 24.

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

Rana Madani  1 , Kalypso Karastergiou, Nicola C Ogston, Nazar Miheisi, Rahul Bhome, Nora Haloob, Garry D Tan, Fredrik Karpe, James Malone-Lee, Majid Hashemi, Marjan Jahangiri, Vidya Mohamed-Ali
Affiliations

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

Rana Madani et al. Am J Physiol Endocrinol Metab. 2009 Jun.

Abstract

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.

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Figures

Fig. 1.
Fig. 1.
Monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and regulated on activation, normal T cell expressed and secreted (RANTES) concentrations in vivo in lean and obese subjects. Fasting arterial and superficial epigastric venous concentrations of RANTES, MCP-1, and IL-6 in lean (n = 11) and obese (n = 8) subjects are shown. Data are shown for individual subjects. Comparisons were carried out by Wilcoxon test, and the P value is shown. MCP-1 concentration in lean (A) and obese (B) subjects, IL-6 concentration in lean (C) and obese (D) subjects, and RANTES concentration in lean (E) and obese (F) subjects are shown.
Fig. 2.
Fig. 2.
Adipose tissue depot-specific differences in the release of cytokines in obese subjects by protein array. With conditioned media from adipose tissue from bariatric (n = 2) and cardiac (n = 3) surgery patients, ∼19 of a possible 36 cytokines were detectable in human adipose tissue culture supernatants. Growth-related protein α (GROα), IL-6, IL-8, macrophage migration inhibitory factor (MIF), and type 1 plasminogen activator inhibitor (PAI)-1 had densities above 50% of the positive control. Positive control spots were assigned a value of 100%, and other spots are shown relative to this. Spots with densities <10% of the positive control were considered negative. RANTES release from gastric fat pad (GFP) was highest, compared with that from the other depots. Histogram shows mean optical density of the spots expressed as % of positive control of the results from the 5 patients; representative blots obtained from 1 bariatric and 1 cardiac surgery patient are shown at bottom. PC, positive control; Om, omental; SC, subcutaneous; Epi, epicardial; G-CSF, granulocyte colony-stimulating factor; sICAM-1, soluble ICAM-1; IL-1RA, IL-1 receptor antagonist.
Fig. 3.
Fig. 3.
Adipose tissue depot-specific differences in the release of RANTES ex vivo. Data are shown as means ± 95% confidence intervals. Exact numbers of samples used per depot are shown. Comparisons were made by Wilcoxon test; significant P values are shown. Release is expressed as picograms of RANTES per gram of adipose tissue per hour at 37°C and 5% CO2.
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