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Departments of Clinical Pharmacology (D.G.H., G.S., M.W.) and Medicine III (K.S., M.W., B.L.), Division of Endocrinology and Metabolism, and Department of Surgery (G.P.), Division of General Surgery, Medical University of Vienna, 1090 Vienna, Austria
Address all correspondence and requests for reprints to: Bernhard Ludvik, M.D., Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Allgemeines Krankenhaus Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria. E-mail: bernhard.ludvik{at}meduniwien.ac.at.
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Abstract |
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Objectives: In this study we investigated whether plasma visfatin concentrations are altered by weight loss in patients with obesity.
Design and Patients: In a prospective study, fasting plasma visfatin, leptin, and adiponectin concentrations were measured before and 6 months after gastric banding in 31 morbidly obese patients aged 40 ± 11 yr with a body mass index (BMI) of 46 ± 5 kg/m2. Fourteen healthy subjects aged 29 ± 5 yr with a BMI less than 25 kg/m2 served as controls.
Results: Visfatin plasma concentrations were markedly elevated in obese subjects (0.037 ± 0.008 µg/ml), compared with controls (0.001 ± 0.000 µg/ml, P < 0.001). Gastric banding reduced BMI to 40 ± 5 kg/m2, visfatin to 19.2 ± 10.9 ng/ml, and leptin from 39.0 ± 12.4 to 29.7 ± 10.0 ng/ml and increased adiponectin from 0.015 ± 0.007 to 0.017 ± 0.007 µg/ml (all P < 0.05) after 6 months. Insulin sensitivity as estimated by the homeostasis model assessment insulin resistance index was unchanged from 5.8 ± 3.1 to 4.6 ± 1.9 (P = 0.13), but individual changes of insulin resistance and visfatin were significantly associated (P < 0.05, r = –0.43).
Conclusions: Elevated plasma visfatin concentrations in morbidly obese subjects are reduced after weight loss. This may be related to changes in insulin resistance over time.
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Introduction |
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Obesity is associated with altered adipocytokine concentrations. Plasma leptin concentrations correlate with body mass index (BMI) and several other indicators of body composition (3, 4). Conversely, the collagen-like protein adiponectin is reduced in obese patients (5). Thus, weight changes exert major influences on circulating adipocytokine concentrations. It is currently unclear whether visfatin represents a marker of adipocyte mass or function or may also exert a regulatory role in glucose metabolism. Furthermore, there is no reference range of plasma visfatin concentrations established and its relationship to changes in body weight is unknown.
We therefore performed the present study to characterize the effects of weight loss after gastric banding surgery on circulating plasma visfatin. Leptin and adiponectin concentrations were quantified as control markers in this prospective, open-labeled, cohort study. An unmatched group of healthy subjects were recruited as controls.
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Subjects and Methods |
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Thirty-one subjects (28 females and three males) aged 40 ± 11 yr (range 19–59 yr) with a BMI of 40 kg/m2 or greater were consecutively recruited among patients who attended the Department of Surgery, Medical University of Vienna, for bariatric surgery. Standardized laparoscopic adjustable gastric banding was performed by the same team of surgeons. Patient characteristics are shown in Table 1
. Subjects with the following conditions were excluded from the study: presence of type 2 diabetes mellitus, history of myocardial infarction during the last 6 months, any malignancy, chronic kidney or liver disease, seizure, obesity caused by an endocrine disorder, psychiatric disorders, current pregnancy, or breast-feeding. Seven male and seven female (29 ± 5 yr; range 24–42 yr) healthy subjects who were not matched with the intervention group for age or sex and who had a BMI less than 25 kg/m2 served as controls and were recruited from a database of healthy volunteers at the Department of Clinical Pharmacology. The study was approved by the Ethics Committee of the Medical University of Vienna. All subjects gave written informed consent before study entry.
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Measurement of visfatin, leptin, and adiponectin
Plasma samples were stored at –70 C until analysis. Visfatin was analyzed using a commercially available ELISA kit (Phoenix Peptides, Karlsruhe, Germany), and total leptin and adiponectin were determined by RIAs (human leptin/adiponectin RIA kit; Linco Research, St. Charles, MO) with an inter- and intraassay coefficient of variation of less than 6% for all assays.
Statistical analyses
Nonparametric tests were performed for comparisons between time points using the Statistica software package (release 6.1; Statsoft Inc., Tulsa, OK). Pearson’s correlation was used for calculation of associations between variables and multiple linear regression analysis with 
visfatin as dependent variable and changes in BMI, HOMA, insulin, glucose, leptin, adiponectin, and waist circumference as independent variables for determination of independent predictors for changes in visfatin. The Wilcoxon matched-pairs test and the Mann-Whitney U test were used for comparisons within and between groups, respectively. P 
0.05 was considered significant. Values are expressed as means ± SD unless indicated otherwise.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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). At baseline there was no relationship between visfatin and any outcome parameter, but leptin was correlated with HOMA (P = 0.03, r = 0.44) and adiponectin (P < 0.01, r = 0.55) and adiponectin with HOMA (P = 0.04, r = 0.41). Six months after surgery, all but one subject had lost weight, which resulted in a significantly decreased BMI, weight, waist circumference, and percent body fat mass (from 49 ± 3 to 46 ± 3% in women and from 39 ± 2 to 37 ± 2% in men) in the group of obese patients (Table 2). This was paralleled by a decrease in visfatin and leptin concentrations and increased plasma adiponectin (Table 2). However, adipocytokine concentrations were not normalized to levels seen in healthy subjects. Changes in visfatin were correlated with changes in BMI (Table 3), weight (P < 0.01, r = 0.64), waist circumference (P < 0.01, r = –0.43), and HOMA. Gastric banding did not affect fasting glucose, insulin (Table 2) or the HOMA insulin resistance index, which was unchanged from 5.8 ± 3.1 before surgery to 4.6 ± 1.9 after 6 months (P = 0.13). There was no relationship between changes in the HOMA insulin resistance index with adipocytokines except for plasma visfatin (Table 3). Multiple linear regression revealed that the change in insulin was the best independent predictor for changes in visfatin. Other independent predictors were changes in BMI and HOMA (Table 4).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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There is preliminary evidence that visfatin might be involved in the development of the metabolic syndrome in obesity (1). The fact that plasma visfatin increases after a high-fat diet in mice further suggests an important role in hyperlipidemia-induced insulin resistance. Cell culture experiments in which recombinant visfatin promoted the accumulation of fat through the activation of glucose transport and lipogenesis are consistent with this assumption (1).
Modulation of insulin action by adipocytokines has been assumed to contribute to the development of obesity-associated insulin resistance (7). Importantly, only visfatin has been identified to exert a direct effect on insulin-receptor signaling among the adipocytokines under study (1). This is compatible with our finding that changes in insulin sensitivity by weight loss were correlated with changes in plasma visfatin but not with leptin or adiponectin. This interesting notion is, however, limited by the fact that improvement in insulin resistance was small during the observation period and did not reach statistical significance. Thus, a longer observation of weight loss might be required to confirm this finding.
Weight loss after gastric banding surgery and changes in leptin and adiponectin were in good agreement with previous studies (8, 9, 10, 11, 12). This consistent finding results from decreased energy intake rather than nutrient malabsorption (13). However, the mechanisms by which long-term weight loss is achieved, often in the absence of decreased appetite, are not well understood. Alterations of circulating adipocytokines may thus contribute to continued weight loss (14).
Generation and clearance of visfatin are not characterized yet. In particular, the source of plasma visfatin is unclear and extrapolation of our results to patients with different metabolic diseases is therefore difficult. Furthermore, it is under debate whether visfatin synthesis is up-regulated in obesity. Whereas some data suggest that visfatin is directly linked to body weight (2) and the development of the metabolic syndrome (1), others have failed to detect a relationship between the metabolic syndrome and visfatin (15). Finally, the time course of normalization of visfatin plasma concentrations after weight loss is unknown. In addition, continued derangements in glucose homeostasis or an altered lipid profile may exert profound influences on the release of visfatin from visceral and sc adipocytes.
Despite substantial weight loss, no change in HOMA was detectable. This is surprising but in agreement with other studies in which ghrelin, leptin, or adiponectin was measured during an observation period of at least 1 yr (16, 17, 18), and no correlation between changes in adipocytokines and HOMA was found (17, 19, 20). Furthermore, stratification for sex did not influence our results. On the other hand, our data might be influenced by a selection bias within the Caucasian population under study, and the limited sample size prevents the identification of small effects.
In summary, weight loss after gastric surgery lowers increased circulating visfatin concentrations in morbidly obese subjects. The relationship between individual changes in visfatin and insulin sensitivity in these patients indicates that visfatin may be involved in the beneficial effect of weight loss on the improvement of insulin resistance.
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Footnotes |
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First Published Online January 31, 2006
Abbreviations: BMI, Body mass index; HOMA, homeostasis model assessment.
Received October 12, 2005.
Accepted January 25, 2006.
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References |
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or adiponectin? Hepatology 40:46–54[CrossRef][Medline]This article has been cited by other articles:
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E. Ingelsson, M. G. Larson, C. S. Fox, X. Yin, T. J. Wang, I. Lipinska, K. M. Pou, U. Hoffmann, E. J. Benjamin, J. F. Keaney Jr., et al. Clinical Correlates of Circulating Visfatin Levels in a Community-Based Sample Diabetes Care, May 1, 2007; 30(5): 1278 - 1280. [Full Text] [PDF]
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