Leptin and the Proinflammatory State Associated with Human Obesity
Chris J. Hukshorn,
Jan H. N. Lindeman,
Karin H. Toet,
Wim H. M. Saris,
Paul H. C. Eilers,
Margriet S. Westerterp-Plantenga and
Teake Kooistra
NUTRIM, Department of Human Biology, Maastricht University (C.J.H., W.H.M.S., M.S.W.-P.) 6200 MD Maastricht, The Netherlands; Gaubius Laboratory, TNO Prevention and Health (J.H.N.L., K.H.T., T.K.), 2301 CE Leiden, The Netherlands; and Departments of Vascular Surgery (J.H.N.L.) and Medical Statistics (P.H.C.E.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands
Address all correspondence and requests for reprints to: Dr. Jan H. N. Lindeman, Department of Vascular Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: lindeman{at}lumc.nl.
It has been suggested that elevated leptin levels underlie thelow grade proinflammatory state in human obesity. We reasonedthat if elevated leptin levels are an important factor in theproinflammatory state in obesity, then exogenous leptin administrationduring weight loss should counteract the concurrent beneficialeffects of weight loss on the proinflammatory state. We thereforedetermined whether long-acting pegylated recombinant leptin(PEG-OB) prevents the decrease in cellular and humoral inflammationparameters during a very low calorie diet in healthy overweightyoung men. Except for B cells, PEG-OB treatment did not influencethe decline in total leukocyte count and mononuclear subfractionsduring the diet. Weight loss decreased the humoral inflammationparameters TNF, tissue plasminogen activator, and von Willebrandfactor (P < 0.05), but in combination with PEG-OB treatment,a significant decrease was shown for inflammation markers asa whole (P < 0.014) and that of the individual parameterstissue plasminogen activator, von Willebrand factor, plasminogenactivator 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 proinflammatoryaction of leptin. Although PEG-OB treatment significantly increasedweight loss (P < 0.03), the data do not support a proinflammatoryrole of leptin in human obesity.
This work was supported by a grant from The Netherlands HeartFoundation (NHS 97.100).
C.J.H. and J.H.N.L. contributed equally to this work and shouldboth be considered as first authors.
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, 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. 
