Effect of hyperinsulinemia and very-low-calorie diet on interstitial cytokine levels in subcutaneous adipose tissue of obese women.
Type 2 diabetes and obesity are associated with an enhanced release of a number of adipocytokines. Hyperinsulinemia, frequently present in type 2 diabetes and obesity, might be one of the drivers of the enhanced production of adipocytokines. The aim of this study was to investigate the interstitial levels of cytokines in subcutaneous adipose tissue (SCAT) in response to hyperinsulinemia and the effect of weight-reducing hypocaloric diet on this regulation in obese subjects. Thirteen obese premenopausal women participated in the study. Concentrations of seven cytokines were measured in plasma and in AT interstitial fluid collected by microdialysis during a euglycemic-hyperinsulinemic clamp and during control infusion of physiological saline. A subgroup of six women underwent a 4-wk very-low-calorie diet (VLCD). Microdialysis during the clamp was performed before and at the end of VLCD. Hyperinsulinemia induced an increase of monocyte chemoatractant protein (MCP-1) and IL-6 SCAT interstitial and plasma levels and elevated IL-8 levels in SCAT. The relative changes of IL-6 levels in the dialysate correlated with changes of IL-8 and MCP-1. The interstitial and plasma levels of IL-1β, IL-10, TNFα, and plasminogen activator inhibitor (PAI-1) remained unchanged in response to hyperinsulinemia. VLCD resulted in enhancement of the hyperinsulinemia-induced augmentation of MCP-1, IL-6, and IL-8 interstitial levels. In conclusion, hyperinsulinemia upregulates the interstitial levels of MCP-1, IL-6, and IL-8 in SCAT in obese women, whereas it does not affect IL-1β, IL-10, TNFα, and PAI-1 levels. Hypocaloric diet associated with weight reduction enhances the hyperinsulinemia-induced upregulation of MCP-1, IL-6, and IL-8 in SCAT.
Siklova-Vitkova
Michaela
M
Sport Medicine Dept., Third Faculty of Medicine, Charles University in Prague, Ruska 87, 100 00 Prague, Czech Republic. mysak.bob@centrum.cz
Polak
Jan
J
Klimcakova
Eva
E
Vrzalova
Jindra
J
Hejnova
Jindra
J
Kovacikova
Michaela
M
Kovacova
Zuzana
Z
Bajzova
Magda
M
Rossmeislova
Lenka
L
Hnevkovska
Zuzana
Z
Langin
Dominique
D
Stich
Vladimir
V
D000328:Adult; D031204:Caloric Restriction; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000378:metabolism; D017551:Microdialysis; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8