Leptin and the proinflammatory state associated with human obesity.
It has been suggested that elevated leptin levels underlie the low grade proinflammatory state in human obesity. We reasoned that if elevated leptin levels are an important factor in the proinflammatory state in obesity, then exogenous leptin administration during weight loss should counteract the concurrent beneficial effects of weight loss on the proinflammatory state. We therefore determined whether long-acting pegylated recombinant leptin (PEG-OB) prevents the decrease in cellular and humoral inflammation parameters during a very low calorie diet in healthy overweight young men. Except for B cells, PEG-OB treatment did not influence the decline in total leukocyte count and mononuclear subfractions during the diet. Weight loss decreased the humoral inflammation parameters TNFalpha, tissue plasminogen activator, and von Willebrand factor (P < 0.05), but in combination with PEG-OB treatment, a significant decrease was shown for inflammation markers as a whole (P < 0.014) and that of the individual parameters tissue plasminogen activator, von Willebrand factor, plasminogen activator inhibitor type 1, and intercellular adhesion molecule-1 (P < 0.05). The increase in C-reactive protein levels (P < 0.05) was the sole indication for a humoral proinflammatory action of leptin. Although PEG-OB treatment significantly increased weight loss (P < 0.03), the data do not support a proinflammatory role of leptin in human obesity.
Hukshorn
Chris J
CJ
NUTRIM, Department of Human Biology, Maastricht University, 6200 MD Maastricht, The Netherlands.
Lindeman
Jan H N
JH
Toet
Karin H
KH
Saris
Wim H M
WH
Eilers
Paul H C
PH
Westerterp-Plantenga
Margriet S
MS
Kooistra
Teake
T
D000328:Adult; D004038:Diet, Reducing; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007279:Injections, Subcutaneous; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood*; D007958:Leukocyte Count; D008297:Male; D009000:Monocytes / Q000473:pathology; D009765:Obesity / Q000097:blood* / Q000150:complications* / Q000178:diet therapy; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D015431:Weight Loss; D014841:von Willebrand Factor / Q000378:metabolism
D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C484843:pegylated leptin; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D011092:Polyethylene Glycols; D010959:Tissue Plasminogen Activator