The relation between body iron stores and adipose tissue function in patients with manifest vascular disease

• Published in: European journal of clinical investigation 2013-12, Vol.43 (12), p.1240-1249
• Main Authors: Westerink, Jan, Olijhoek, Jobien K., Koppen, Arjen, Faber, Daniël R., Kalkhoven, Eric, Monajemi, Houshang, van Asbeck, B. Sweder, van der Graaf, Yolanda, Visseren, Frank L. J.
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - metabolism; adiponectin; Adiponectin - metabolism; Adiponectin - secretion; Adipose Tissue - physiology; adipose tissue function; Atherosclerosis - blood; Atherosclerosis - physiopathology; Case-Control Studies; Cells, Cultured; Female; Ferric Compounds - pharmacology; Ferritins - metabolism; Free Radical Scavengers - pharmacology; Humans; Interleukin-6 - biosynthesis; iron; Iron Chelating Agents - pharmacology; Male; Metabolic Syndrome - blood; Metabolic Syndrome - physiopathology; Middle Aged; obesity; Obesity, Abdominal - blood; Obesity, Abdominal - physiopathology; Prospective Studies
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/eci.12165

Background We investigated whether plasma ferritin levels through the pro‐inflammatory effects of free iron are associated with adipose tissue dysfunction in a relevant population of patients with manifest vascular disease who would potentially benefit the most from further aetiological insights. Materials and methods In a cohort of 355 patients with vascular diseases, the association between plasma ferritin and adiponectin levels was quantified using linear regression analysis. Interleukin‐6 and adiponectin levels were measured in medium from pre‐adipocytes and adipocytes after incubation with increasing concentrations of Fe(III)‐citrate and after co‐incubation with iron chelators or radical scavengers. Results Increasing ferritin plasma concentrations were not related to plasma adiponectin levels in patients without (β −0·13; 95% CI −0·30 to 0·04) or with the metabolic syndrome (β −0·04; 95% CI −0·17 to 0·10). Similar results were found in patients who developed a new cardiovascular event in the follow‐up period. In vitro, incubation with increasing concentrations of Fe(III)‐citrate‐induced inflammation in pre‐adipocyte cultures as witnessed by increased IL‐6 secretion at 30 μm Fe(III)‐citrate vs. control (500 ± 98 pg/mL vs. 194 ± 31 pg/mL, P = 0·03). Co‐incubation of pre‐adipocytes with iron chelators or radical scavengers prevented this inflammatory response. Incubation of adipocytes with 30 μm Fe(III)‐citrate did not influence adiponectin secretion compared with control. Conclusions In patients with vascular disease, there is no association between plasma ferritin and adiponectin levels. In vitro, free iron induces an inflammatory response in pre‐adipocytes, but not in adipocytes. This response was blocked by co‐incubation with iron chelators or radical scavengers. Adiponectin secretion by adipocytes was not influenced by free iron.