Interleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss.
OBJECTIVE
Interleukin (IL)-18 is associated with obesity, insulin resistance, and cardiovascular disease. The present study compared 1) IL-18 in adipocytes versus stromal vascular (SV) cells, 2) IL-18 in plasma and adipose tissue (AT) in obese versus lean subjects, and 3) IL-18 in plasma, AT, and skeletal muscle (SM) in obese subjects after weight loss.


METHODS
At baseline, plasma and AT IL-18 in 23 obese subjects were compared with that in 12 lean subjects. The obese subjects were submitted to a 15-week life-style intervention (hypocaloric diet and daily exercise) after which plasma samples, AT, and SM biopsies were obtained. Analyses were performed by ELISA and RT-PCR respectively.


RESULTS
IL-18 expression in isolated adipocytes was approximately 2% of that in SV cells. Plasma IL-18 was higher in obese subjects (P < 0.001) and associated with insulin resistance (HOMA; P < 0.001). AT expression of IL-18, CD14, and CD68 was higher in obese (P < 0.01). The intervention reduced body weight (P < 0.001), plasma IL-18 (P < 0.001), and increased insulin sensitivity (HOMA; P < 0.05). AT and SM expression of IL-18 remained unchanged after the intervention. Changes in plasma IL-18 were associated with changes in insulin sensitivity (P < 0.05) but not with BMI or AT expression of IL-18.


CONCLUSIONS
Plasma IL-18 is associated with changes in insulin resistance and reduced after weight loss. AT expression of IL-18 is increased in obesity but not affected by weight loss, indicating that changes in plasma IL-18 are related to insulin resistance rather than changes in obesity per se.
Bruun
Jens M
JM
Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus, DK-8000 Aarhus C, Denmark. Jens.Bruun@ki.au.dk
Stallknecht
Bente
B
Helge
Jørn W
JW
Richelsen
Bjørn
B
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D004035:Diet Therapy; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D020382:Interleukin-18 / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000097:blood* / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D017154:Stromal Cells / Q000378:metabolism; D013851:Thinness / Q000097:blood / Q000378:metabolism; D015431:Weight Loss / Q000502:physiology*
D018836:Inflammation Mediators; D020382:Interleukin-18