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Relationship between Adipocyte Size and Adipokine Expression and Secretion

Else Kröner-Fresenius-Center for Nutritional Medicine of the Technical University Munich (T.S., C.A.-H., H.H.), D-85350 Freising, Germany; and the German Diabetes Clinic, German Diabetes Center (C.H.), Leibniz Center at Heinrich-Heine-University Düsseldorf, D-40225 Düsseldorf, Germany

Address all correspondence and requests for reprints to: Thomas Skurk, Else Kröner-Fresenius-Centre for Nutritional Medicine, Technical University Munich, Am Forum 5, D-85350 Freising-Weihenstephan, Germany. E-mail: nutritional.medicine{at}wzw.tum.de.

Context: Adipocytes are known to release a variety of factors that may contribute to the proinflammatory state characteristic for obesity. This secretory function is considered to provide the basis for obesity-related complications such as type 2 diabetes and atherosclerosis.

Objective: To get a better insight into possible underlying mechanisms, we investigated the effect of adipocyte size on adipokine production and secretion.

Design, Patients, and Main Outcome Measures: Protein secretion and mRNA expression in cultured adipocytes separated according to cell size from 30 individuals undergoing elective plastic surgery were investigated.

Results: The mean adipocyte volume of the four fractions ranged from 205 ± 146 to 1.077 ± 471 pl. There were strong linear correlations for the secretion of adipokines over time. Secretion of leptin, IL-6, IL-8, TNF-, monocyte chemoattractant protein-1, interferon--inducible protein 10, macrophage inflammatory protein-1ß, granulocyte colony stimulating factor, IL-1ra, and adiponectin was positively correlated with cell size. After correction for cell surface, there was still a significant difference between fraction IV (very large) and fraction I (small cells), for leptin, IL-6, IL-8, monocyte chemoattractant protein-1, and granulocyte colony-stimulating factor. In contrast, antiinflammatory factors such as IL-1ra and adiponectin lost their association after correction for cell surface area comparing fraction I and IV. In addition, there was a decrease of IL-10 secretion with increasing cell size.

Conclusions: The results clearly suggest that adipocyte size is an important determinant of adipokine secretion. There seems to be a differential expression of pro- and antiinflammatory factors with increasing adipocyte size resulting in a shift toward dominance of proinflammatory adipokines largely as a result of a dysregulation of hypertrophic, very large cells.

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