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*Gene*GEO Profiles
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Medline Plus Health Information
*Nutrition
*Weight Loss Surgery
The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 8 4062-4068
Copyright © 2004 by The Endocrine Society

Macrophage Inhibitory Factor, Plasminogen Activator Inhibitor-1, Other Acute Phase Proteins, and Inflammatory Mediators Normalize as a Result of Weight Loss in Morbidly Obese Subjects Treated with Gastric Restrictive Surgery

F. M. H. van Dielen, W. A. Buurman, M. Hadfoune, J. Nijhuis and J. W. Greve

Department of General Surgery, Nutrition Research Institute Maastricht and University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands

Address all correspondence and requests for reprints to: F. M. H. van Dielen, Department of General Surgery, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. E-mail: f.vandielen{at}ah.unimaas.nl.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Obesity is demonstrated to be associated with an enhanced inflammatory state, which is suggested to be a cause for the development of obesity-related morbidity. It was hypothesized that a decrease in body weight in morbid obese subjects would lead to a reduction of the inflammatory state in these subjects.

Weight loss was achieved by gastric restrictive surgery in 27 morbidly obese patients. Preoperative as well as 3-, 6-, 12-, and 24-month postoperative plasma concentrations of inflammatory mediators macrophage inhibitory factor, plasminogen activator inhibitor-1, lipopolysaccharide binding protein, {alpha}-1 acid glycoprotein, C-reactive protein, soluble TNF{alpha} receptors 55 and 75, and leptin were measured.

Macrophage inhibitory factor levels remained low normal for 6 months, during weight loss, after which they significantly increased to normal levels at 24 months postoperatively. The other inflammatory mediators remained elevated up to minimally 3 months postoperatively; thereafter they decreased significantly. Both TNF{alpha} receptors remained elevated up to at least 12 months postoperatively to decrease significantly at 2 yr postoperatively.

This study demonstrates that during weight loss, after gastric restrictive surgery, inflammatory mediators remain elevated for at least 3 months postoperatively, suggesting initially an ongoing inflammatory state. However, 2 yr after surgery, the inflammatory mediators reach near normal values.

These findings may be an explanation for the reduced comorbidity seen in morbidly obese patients after gastric restrictive surgery.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
OBESITY IS ASSOCIATED with decreased longevity and increased morbidity due to a variety of disorders such as type 2 diabetes mellitus, cardiovascular diseases, hypertension, and hyperlipidemia (1). The basis of the relation between obesity and the development of these disorders is still unclear. Recent data show enhanced circulating levels of inflammatory mediators in obese individuals (2, 3). These observations are interesting in the context of a suggested pathophysiological role for inflammatory mediators (such as TNF{alpha}) in the development of the obesity-related morbidity such as insulin resistance and cardiovascular disease (4). Moreover, in vivo and in vitro studies have indicated an involvement of macrophage inhibitory factor (MIF) in the pathophysiology of insulin resistance (5).

In a previous study, we demonstrated a correlation between levels of inflammatory mediators, acute-phase proteins, and body weight (6). Although a causative relation has not been found yet, it is suggested that elevated levels of C-reactive protein (CRP) are prognostic for the development of cardiovascular disease (7, 8). Also, other proteins related to inflammation are suggested to be associated with the development of obesity-related diseases such as plasminogen activator inhibitor-1 (PAI-1) and MIF (9, 10).

Increased plasma levels of inflammatory markers and acute phase proteins were present without physical evidence of acute or chronic inflammation in morbidly obese (6). It is tempting to speculate that the metabolic stress caused by morbid obesity is responsible for the acute phase response seen in these patients.

Several studies demonstrated that weight loss leads to reduced obesity-related comorbidity (11, 12, 13). Based on the above-mentioned findings, we hypothesized that weight loss, after gastric restrictive surgery, resulting in a reduction of the metabolic stress, leads to a decrease in inflammatory mediators and acute-phase proteins in morbidly obese subjects.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
A total of 27 consecutive subjects, which were admitted to the Surgical Department of the University Hospital Maastricht for surgical treatment of morbid obesity, were included in the study. The majority of these patients (n = 26) underwent a primary operation for morbid obesity [vertical banded gastroplasty (VBG, n = 11) or LapBand (n = 15)]. In one patient a gastric bypass was performed because of weight regain as a result of a staple line disruption after initial VBG. All subjects were otherwise healthy according to history, clinical examination, and routine laboratory findings. In particular, none of the studied subjects showed evidence of acute or chronic inflammatory disease. Characteristics of the subjects are presented in Table 1Go. Weight loss was expressed as percentage excess weight loss (EWL), which could be calculated with the following formula: (preoperative weight – weight after reduction)/(preoperative weight – ideal weight) * 100%.


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  		TABLE 1. Characteristics of the study group

 
Blood samples were collected after at least 8 h fasting, using evacuated blood collection tubes containing EDTA, at the day of admission to the hospital; 1 d before surgery; and 3, 6, 12, and 24 months after surgery. The blood samples were immediately put on melting ice and plasma was prepared by centrifugation at 1400 x g for 10 min at 4 C. The plasma was centrifuged at 2700 x g for 10 min at 4 C and stored in aliquots at –80 C. All participants gave written informed consent. The study was approved by the ethical committee of the University Hospital Maastricht.

VBG

In our hospital the procedure was performed as initially described by Mason (14). Briefly, a small pouch of the stomach (approximately 15–20 ml) was created with a four-row linear stapler (TA-90B, United States Surgical Corp., Norwalk, CT) precisely to the angle of His, and a Dacron band of 5.0 cm in circumference placed through the window formed by a circular stapler (Premium Plus CEEA 31 mm, United States Surgical Corp.), leaving a very small opening for food to pass from the small pouch to the remaining stomach. Because of the small capacity of the gastric pouch, the amount of ingested food is considerably limited, leading to extensive weight loss (15).

Laparoscopic gastric banding (LapBand)

The LapBand (BioEnterics, Inamed, Carpinteria, CA) is a new surgical technique to reduce body weight. The LapBand is made of soft silicone and equipped with an elastic balloon that can be inflated to the desired volume by means of injection postoperatively. After inflation the outlet diameter will be reduced, leading to diminished food intake and consequently to weight loss. This procedure was initially performed as described by Belachew et al. (16). In short, the LapBand was placed laparoscopically around the stomach. For definitive positioning of the band, a 15-ml calibration balloon advanced by the anesthetist and pulled up to the gastroesophageal junction was placed right below the cardia. Under this balloon the band was closed, and with three or four sutures, the ventral aspect of the greater curvature of the stomach is fixed to the pouch to ensure a stable anterior position of the band. Six weeks postoperatively the LapBand was insufflated when weight loss was insufficient (less than 6 kg). During the study period, the LapBand was insufflated as often as needed, up to a maximum of 4.5 ml, to induce sufficient weight loss (approximately 1 kg weight loss per week).

Reagents and materials

Monoclonal antibodies (mAbs) specifically directed against soluble TNF{alpha} receptor 55 (TNFR55) and soluble TNF{alpha} receptor 75 (TNFR75) were obtained as described elsewhere (17). Polyclonal rabbit antisera anti-TNFR55 and anti-TNFR75 were obtained by immunizing rabbits with TNFR55 and TNFR75, respectively. Both mAbs 4G1 and 4F8 to leptin, were kindly provided by Dr. R. Devos (Hoffmann La-Roche, Welwyn Garden City, UK).

Human recombinant lipopolysaccharide binding protein (LBP), used as standard, was produced by transfected Chinese hamster ovary cells, kindly provided by Dr. P. Tobias (Research Institute of Scripps Clinic, La Jolla, CA). Polyclonal antibodies to human LBP were obtained by immunizing rabbits with human LBP. Human CRP was obtained from Dade Behring (Deerfield, IL); rabbit antihuman CRP and rabbit antihuman CRP-horseradish peroxidase were purchased from Dako (Glostrup, Denmark).

Human {alpha}-1 acid glycoprotein (AGP) was obtained from Sigma (St. Louis, MO) and rabbit antihuman AGP from Dako. BSA was purchased from Sigma. Recombinant human leptin and MIF, a mAb antihuman MIF and a polyclonal antibody against human MIF were purchased from R&D Systems (Minneapolis, MN). Peroxidase-conjugated streptavidin was purchased from Dakopatts (Glostrup, Denmark) and 3, 3', 5, 5'-tetramethylbenzidine (TMB) substrate from Kirkegaard & Perry Laboratories (Gaithersburg, MD). Immunomaxisorp plates (Nunc, Roskilde, Denmark) were used for ELISAs.

Immunoassays

Plasma concentrations of both soluble TNF{alpha} receptors, leptin, LBP, CRP, AGP, MIF, and PAI-1 concentrations were measured using sandwich ELISAs. TNFR55, TNFR75, LBP, CRP, and AGP were quantified as described elsewhere (6, 17, 18). The ELISAs for TNFR55, TNFR75, and LBP had a detection limit of approximately 100 pg/ml. The detection limit for CRP and AGP was approximately 10 pg/ml. The detection of plasma leptin levels was described elsewhere (19). In short, 96-wells plates were coated overnight at 4 C with an antihuman leptin antibody and diluted plasma samples as well as a dilution series of recombinant human leptin were added to the plate. Bound leptin was detected with a second antihuman leptin antibody, followed by peroxidase-conjugated goat antimurine IgA and TMB. The detection limit of this leptin assay is 0.04 ng/ml.

PAI-1 concentrations were measured using an ELISA, kindly provided by Dr. T. Kooistra (Leiden University Medical Center, Leiden, The Netherlands). In short, microtiter strip plates were coated with a high-affinity mAb PAI-1 3–3B against PAI-1. Detection for PAI-1 was carried out using a horseradish peroxidase-labeled antibody rabbit anti-PAI-1 followed by TMB. For MIF quantification, plates were coated with a mAb against human MIF. After adding the samples, detection was carried out with a biotinylated mAb against human MIF, followed by peroxidase-conjugated streptavidin and substrate.

All plasma samples were analyzed in the same run. When plasma concentrations exceeded the upper detection limit of the assay, samples were additionally diluted and analyzed in a separate run with an overlap to correct for interassay variation. The intra- and interassay coefficients of variance of the various assays were less than 10%.

Statistical analysis

Data are given as mean and SD except for MIF and PAI-1 because of no normal distribution. Statistical analysis was performed nonparametrically and two sided. The Wilcoxon signed ranks test was used to analyze differences between preoperative and postoperative values, within the morbidly obese subjects.

Pearson correlation coefficients were computed between body mass index (BMI) and leptin on the different time points. Statistical analyses were performed using the SPSS 10.0.7 statistical package (SPSS Inc. (Chicago, IL). P < 0.05 was denoted as statistically significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The effect of weight loss on plasma leptin and MIF

Table 1Go summarizes the characteristics of the total of 27 morbidly obese patients studied. No differences in preoperative BMI was observed between both types of operation technique. As shown in Fig. 1AGo, BMI significantly decreased after surgery from 46.7 ± 5.8 kg/m2 (mean ± SD) preoperatively to 33.0 ± 4.8 at 24 months postoperatively (P < 0.001). BMI decreased most strikingly in the first 3 months postoperatively. As shown in Table 2Go, the relative EWL also was more in the period 0–3 months, compared with 4–6 months postoperatively. In the following 7- to 12-month period, the increase of EWL was significantly lower in comparison with the 0- to 6-month period. From 12 to 24 months, postoperative EWL hardly changed.



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  		FIG. 1. Effect of bariatric surgery on BMI and plasma leptin concentration. BMI (A) and plasma leptin concentrations (B) were determined in 27 morbidly obese subjects preoperative as well as after gastric restrictive surgery. BMI and leptin both significantly decreased after gastric restrictive surgery. Values are shown as mean ± SD. *, significantly changed, compared with preoperative values.

 

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  		TABLE 2. The effect of gastric restrictive surgery on EWL

 
In a previous study, we demonstrated a correlation between leptin and body weight (6). To evaluate the effect of weight loss on leptin levels in morbidly obese subjects, leptin was measured. As expected, plasma leptin concentrations decreased significantly postoperatively. Leptin levels decreased from 92.5 ± 31.8 to 52.5 ± 27.3 ng/ml at 3 months, 49.8 ± 28.0 ng/ml at 6 months, and 38.0 ± 25.8 ng/ml at 12 months and slightly increased to 53.9 ± 35.7 ng/ml at 24 months postoperatively. As shown in Fig. 1BGo, the reduction in leptin levels was most pronounced in the first 3 months, in which the strongest decrease in EWL was observed.

In our previous study, we also demonstrated a correlation between body weight and acute-phase proteins. The acute-phase proteins MIF and PAI-1 are, besides leptin, also produced by adipose tissue (20, 21, 22). Next to this, MIF is considered to be related to insulin resistance (5) as well as to the development of atherosclerosis (9). PAI-1 is demonstrated to contribute to the increased susceptibility to atherogenesis, described in insulin-resistant patients with obesity (23, 24). In this context MIF and PAI-1 levels were measured in weight-losing morbidly obese subjects. Interestingly, in contrast to leptin levels, plasma MIF levels remained stable for the first 6 months postoperatively at a relatively low level. Thereafter MIF levels significantly increased to reach levels of lean individuals of 0.71 ± 0.58 ng/ml at 24 months (Fig. 2AGo). PAI-1 levels significantly decreased rapidly after surgery from 23.0 ± 14.0 ng/ml preoperatively to 7.5 ± 4.5 ng/ml at 12 months postoperatively (Fig. 2BGo). PAI-1 levels displayed an initial strong reduction, being restricted to the first 3 months postoperatively. After 12 months PAI-1 levels remained rather stable, although with a wide SD, at 9.2 ± 15.6 ng/ml up to 24 months postoperatively.



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  		FIG. 2. Effect of weight loss on MIF and PAI-1 levels. The effect of weight loss due to gastric restrictive surgery on plasma levels of MIF (A) and PAI-1 (B). Data are depicted as median ± interquartile ranges. *, Significantly changed compared with preoperative values. **, Mean of normal values according to Sasaki et al. (52 ). ***, Median of normal values according to Lehmann et al. (53 ).

 
The effect of weight loss on LBP, CRP, and AGP

In addition, the plasma levels of the acute-phase proteins LBP, CRP, and AGP were measured (Fig. 3Go). LBP levels did not change significantly during the first 6 months postoperatively. However, at 12 and 24 months postoperatively, LBP levels decreased significantly (P < 0.05; 107.6 ± 77.4 and 78.9 ± 39.4 µg/ml, respectively), compared with preoperative values (134.7 ± 98.2). Similarly, CRP levels did not change up to 6 months postoperatively. Only after an EWL of more than 40% could a significant reduction in CRP levels be observed (P < 0.05).



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  		FIG. 3. Effect of weight loss on acute-phase proteins. The effect of weight loss due to gastric restrictive surgery on plasma levels of the acute phase proteins LBP (A), CRP (B), and AGP (C). Data are depicted as mean ± SD. *, Significantly changed, compared with preoperative values. **, Mean of normal values according to Prucha et al. (54 ). ***, Mean of normal values according to van Dielen et al. (6 ).

 
Interestingly, the patterns of the three type I acute-phase protein levels differed. Both LBP and CRP showed a significant and a substantial reduction from 6 months after surgery onward. After 3 months both CRP and LBP levels were enhanced, although not significantly. In contrast, AGP levels displayed a similar pattern to that of PAI-1 levels. The AGP levels were decreased at 3 months after the operation. A significant decrease of 49% was reached at 6 months postoperatively (P < 0.05), compared with preoperative data, whereas from 6 months after surgery onward, AGP levels remained unchanged.

The effect of weight loss on both soluble TNF{alpha} receptors

Both soluble TNF{alpha} receptor levels did not change during the first year postoperatively. However, after 24 months TNFR55 was significantly decreased (P < 0.05), compared with preoperative values, whereas TNFR75 remained unchanged. The levels of both soluble TNF{alpha} receptors at 24 months postoperatively were still significantly higher, compared with levels in lean subjects (6).


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
In this study we investigated the influence of weight loss after surgical treatment of morbid obesity on the levels of inflammatory mediators. Gastric restrictive surgery led to a significantly decreased BMI. In the first 6 months after the operation, the BMI decreased substantially and reached a plateau at approximately 12 months. At this time point, the BMI was still above 30 kg/m2 (the cut-off point of obesity). These data are in line with data of Naslund et al. (25) showing that after VBG the patients were still obese (BMI decreased from 44.4 preoperative to 32.6 kg/m2 4 yr after surgery). Also leptin, which is primarily expressed and released by adipose tissue (26), significantly decreased. On the different time points after gastric restrictive surgery, BMI and leptin were significantly correlated with each other (data not shown), implicating that, in general, leptin is a reliable indicator of fat mass.

Previously it has been demonstrated that inflammatory mediators are elevated in obese subjects (6, 27, 28). In recent studies a regulatory role for leptin on the immune response has been proposed (29, 30, 31, 32). In this context, the elevated plasma leptin concentrations in morbidly obese patients may modulate the immunological homeostasis, leading to increased concentrations of acute-phase proteins and other inflammatory mediators, characteristic for a chronic inflammatory state. However, Hukshorn et al. (33) demonstrated that injections with high concentrations of recombinant leptin, in obese patients with already elevated plasma leptin levels, did not affect plasma levels of different acute-phase proteins, indicating that in obese individuals leptin does not directly regulate acute-phase protein levels.

Another important protein produced by adipose tissue is MIF, an acute-phase protein that is shown in animal models to be released by anterior pituitary cells in response to endotoxin (34). Recent animal and in vitro studies suggested that MIF is linked to the development of atherosclerosis (9, 10). These findings might suggest that high MIF concentrations are to be expected in morbidly obese subjects. In contrast, here it is demonstrated that MIF levels in morbidly obese subjects are low, although still in the normal range, and increase postoperatively with decreasing body weight.

An explanation for these decreased MIF levels in morbidly obese subjects appears to be the reduced insulin sensitivity, often seen in morbidly obese subjects. The intracellular glucose level was found to be critical for the MIF protein content in adipose tissue.

In this context MIF mRNA expression of both epididymal fat pads of Tokushima fatty rats and Wistar fatty rats was found to be down-regulated, whereas plasma MIF levels of Wistar fatty rats increased upon treatment with pioglitazone, an insulin sensitizer (5). These data suggest that the interplay between glucose and insulin is central to the regulation of MIF concentrations, leading to an increase of plasma MIF levels with enhanced insulin sensitivity. Because it is known that, with an increase in body weight, insulin sensitivity decreases (35), these data might explain the unexpected low concentrations of MIF measured in morbidly obese subjects.

Furthermore, MIF is demonstrated to sustain macrophage survival and function by suppressing activation-induced, p53-dependent apoptosis (36). This finding combined with the preoperative low concentrations of MIF found in this report suggest an impaired macrophage function in morbidly obese subjects. If so, this might be an explanation for the observation that morbidly obese patients demonstrate more postoperative complications, compared with lean subjects (37, 38). However, further studies are necessary to unravel the pathophysiological role of MIF in morbidly obese subjects.

Although mainly produced in the stromal cell, besides leptin and MIF, PAI-1 is also adipose tissue derived (36). Mitchell et al. (36) demonstrated that PAI-1 expression was 5-fold higher in the visceral fat that in the sc fat. Next to this, Janssen and Ross (39) demonstrated that during weight loss the reduction in visceral fat was faster than in sc fat. In line with these data, the present results show that PAI-1 levels decreased rapidly with a decrease in body weight.

On the other hand, despite significant weight loss and concurrent decrease of plasma leptin levels, the levels of the acute-phase proteins LBP and CRP and both TNF{alpha} receptors remained elevated up to 6 months or longer. The acute-phase protein AGP, like PAI-1, showed a rapid decrease after surgery. Two years after gastric restrictive surgery, all acute-phase proteins were significantly reduced.

Different explanations can be proposed for the initially sustained elevation of inflammatory mediators. First, the effect of the operation and the subsequent healing process might be a possible explanation for the enhanced inflammatory state during the first 6 months postoperatively. However, various studies demonstrate that the highest CRP levels occur 12–48 h after surgery (40, 41, 42) and will remain elevated only for a period of maximum 12 d postoperatively (42). Second, a nonalcoholic steatohepatitis might be an explanation for the sustained elevation of inflammatory mediators. Rapid weight loss can result in a mild increase in inflammatory lesions (hepatitis) (43). Increased concentration of intracellular fatty acids, as has been observed during rapid weight loss, could explain these inflammatory lesions in the liver after weight loss. Such elevated levels of free fatty acids may be directly toxic for the liver or lead to oxidative stress. However, severe nonalcoholic steatohepatitis and hepatic failure are seldom described after gastroplasty or gastric bypass (44).

A third possible explanation for the prolonged elevation of inflammatory mediators might be an enhanced metabolic stress response due to relative starvation. It is demonstrated in very malnourished anorexia nervosa patients that TNF{alpha} and IL-1ß were elevated, compared with healthy controls. After refeeding these inflammatory mediators returned to normal levels (19, 45, 46, 47). If we assume that extensive weight loss after gastric restrictive surgery is comparable with starvation, this could be an explanation for the prolonged elevation of inflammatory mediators. We consider therefore that from the moment onward that the body weight is stabilized at approximately 12 months postoperatively, the metabolic instability will improve, leading to a reduction in inflammatory mediators. This was reflected by the reduced CRP levels at 24 months after gastric restrictive surgery. Taken together, CRP levels were postoperatively not directly correlated with BMI but rather also influenced by the disturbed metabolism.

Next to the acute-phase proteins, soluble TNFR55 and TNFR75 were measured. In earlier reports, levels of soluble TNF{alpha} receptors were demonstrated to be of value in characterizing an inflammatory response (48, 49). In an earlier report we demonstrated an increase in both soluble TNF{alpha} receptors with increasing body weight (6). Whether this elevation of soluble TNF{alpha} receptor levels is caused by elevated levels of TNF{alpha}, produced by adipocytes, is as yet unknown. If so, soluble TNF{alpha} receptor levels would decrease with decreasing body weight due to a reduction in body fat. However, in this report we demonstrate a sustained elevation, compared with healthy controls, up to 1 yr postoperatively for both soluble TNF{alpha} receptors, despite the weight loss. The fact that the studied subjects were still obese (mean BMI was 33.0 kg/m2), even at 24 months after gastric restrictive surgery, might be an explanation for the sustained elevation of both soluble TNF{alpha} receptors.

An increasing number of studies demonstrate a central role for inflammatory processes in the pathogenesis of cardiovascular disease and insulin resistance (8, 50). Plasma levels of several markers of inflammation have been found to be associated with an increased cardiovascular risk in a variety of clinical settings. Especially CRP and PAI-1 are important prognostic factors for the development of cardiovascular disease (24, 51). As demonstrated in this report, during weight loss due to gastric restrictive surgery, almost all inflammatory mediators measured eventually decrease. Next to this, it is demonstrated by others that after gastric restrictive surgery, obesity-related comorbidities like cardiovascular disease and diabetes mellitus are strongly reduced (12, 13).

So hypothetically the decreased inflammatory mediators after weight loss in morbidly obese patients, as shown in this study, may be related to an improvement of comorbidities in these patients.

In summary, this study demonstrates that after gastric restrictive surgery, BMI and leptin levels significantly decrease, whereas MIF levels increase. Despite the extensive weight loss, both soluble TNF receptors as well as the acute phase proteins LBP and CRP remained elevated up to 6 months postoperatively, suggesting an ongoing inflammatory state in these obese subjects. However, 2 yr after gastric restrictive surgery, when the body weight has stabilized, the levels of all inflammatory mediators were strongly decreased.

Hypothetically this improved metabolic state might be an explanation for the reduced obesity-related comorbidity after successful surgical treatment for morbid obesity.


   Acknowledgments
 
We are indebted to Dr. T. Kooistra (Leiden, The Netherlands) for providing the PAI-1 ELISA kit. We thank Dr. R. Devos (Hoffmann-La Roche, Welwyn Garden City, UK) for providing reagents for the leptin-ELISA.


   Footnotes
 
This work was supported by the AGIKO-stipendium of The Netherlands Organisation of Scientific Research (to F.M.H.v.D.).

Abbreviations: AGP, {alpha}1 Acid glycoprotein; BMI, body mass index; CRP, C-reactive protein; EWL, excess weight loss; LBP, lipopolysaccharide binding protein; mAb, monoclonal antibody; MIF, macrophage inhibitory factor; PAI-1, plasminogen activator inhibitor-1; TMB, 3, 3', 5, 5'-tetramethylbenzidine; TNFR55, TNF{alpha} receptor 55; TNFR75, TNF{alpha} receptor 75; VBG, vertical banded gastroplasty.

Received December 11, 2003.

Accepted May 6, 2004.


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 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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