Effect of hyperinsulinemia and very-low-calorie diet on interstitial cytokine levels in subcutaneous adipose tissue of obese women

doi:10.1152/ajpendo.00086.2009

Effect of hyperinsulinemia and very-low-calorie diet on interstitial cytokine levels in subcutaneous adipose tissue of obese women

Michaela Siklova-Vitkova,¹^,2^,3 Jan Polak,²^,6 Eva Klimcakova,¹^,2 Jindra Vrzalova,⁵ Jindra Hejnova,¹^,2 Michaela Kovacikova,¹^,2 Zuzana Kovacova,¹^,2 Magda Bajzova,¹^,2^,6 Lenka Rossmeislova,¹^,2^,3 Zuzana Hnevkovska,¹^,2^,6 Dominique Langin,¹^,3^,4^,7 and Vladimir Stich¹^,2

¹Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, and Inserm, Toulouse, France; ²Sports Medicine Department, Third Faculty of Medicine, Charles University, Prague, Czech Republic; ³Inserm, U858, Obesity Research Laboratory, Rangeuil Institute of Molecular Medicine, Toulouse, France; ⁴Université Paul Sabatier, Louis Bugnard Institute, Toulouse, France; ⁵Immunoanalytic Laboratory, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic; ⁶Second Internal Medicine Department, Vinohrady Teaching Hospital, Prague, Czech Republic; and ⁷CHU de Toulouse, Laboratory of Biochemistry, Toulouse, France

Submitted 11 February 2009 ; accepted in final form 27 August 2009

Type 2 diabetes and obesity are associated with an enhancedrelease of a number of adipocytokines. Hyperinsulinemia, frequentlypresent in type 2 diabetes and obesity, might be one of thedrivers of the enhanced production of adipocytokines. The aimof this study was to investigate the interstitial levels ofcytokines in subcutaneous adipose tissue (SCAT) in responseto hyperinsulinemia and the effect of weight-reducing hypocaloricdiet on this regulation in obese subjects. Thirteen obese premenopausalwomen participated in the study. Concentrations of seven cytokineswere measured in plasma and in AT interstitial fluid collectedby microdialysis during a euglycemic-hyperinsulinemic clampand during control infusion of physiological saline. A subgroupof six women underwent a 4-wk very-low-calorie diet (VLCD).Microdialysis during the clamp was performed before and at theend of VLCD. Hyperinsulinemia induced an increase of monocytechemoatractant protein (MCP-1) and IL-6 SCAT interstitial andplasma levels and elevated IL-8 levels in SCAT. The relativechanges of IL-6 levels in the dialysate correlated with changesof IL-8 and MCP-1. The interstitial and plasma levels of IL-1β,IL-10, TNF ${alpha}$ , and plasminogen activator inhibitor (PAI-1) remainedunchanged in response to hyperinsulinemia. VLCD resulted inenhancement of the hyperinsulinemia-induced augmentation ofMCP-1, IL-6, and IL-8 interstitial levels. In conclusion, hyperinsulinemiaupregulates the interstitial levels of MCP-1, IL-6, and IL-8in SCAT in obese women, whereas it does not affect IL-1β,IL-10, TNF ${alpha}$ , and PAI-1 levels. Hypocaloric diet associated withweight reduction enhances the hyperinsulinemia-induced upregulationof MCP-1, IL-6, and IL-8 in SCAT.

microdialysis; adipose tissue; adipokines

Address for reprint requests and other correspondence: M. Siklova, Sport Medicine Dept., Third Faculty of Medicine, Charles University in Prague, Ruska 87, 100 00 Prague, Czech Republic (e-mail: mysak.bob{at}centrum.cz).