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Table of Contents   
ORIGINAL RESEARCH  
Year : 2011  |  Volume : 22  |  Issue : 4  |  Page : 537-541
Correlation between leptin and the health of the gingiva: A predictor of medical risk


1 Department of Periodontics, M R Ambedkar Dental College, Bangalore, India
2 Department of Periodontics, A B Shetty Memorial Institute of Dental Sciences, Mangalore, India

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Date of Submission07-Dec-2009
Date of Decision25-May-2010
Date of Acceptance05-Jun-2010
Date of Web Publication26-Nov-2011
 

   Abstract 

Context: Over the past decade, a growing body of scientific evidence has suggested an exquisite association between oral infection and systemic diseases (e.g. atherosclerosis, cardiovascular diseases, premature or low birth weight babies, pulmonary diseases, etc.) and also between systemic diseases (e.g. arthritis, diabetes, HIV infection and osteoporosis) and oral and craniofacial diseases and disorders. Leptin is a hormone secreted by the adipocytes in varying quantities and regulates the body weight. The present study was undertaken in the context of knowing the role of leptin in the inflammatory process occurring in the gingiva as the disease progressed from gingivitis to periodontitis.
Aims: The present study was done to correlate the concentrations of leptin and interleukin (IL)-6 within the gingiva in healthy, gingivitis and periodontitis groups of patients and to correlate gingival leptin and IL-6 concentrations with plasma leptin and IL-6 concentrations in the healthy, gingivitis and periodontitis groups of patients.
Settings and Design: This was a cross-sectional study and was carried out on the patients from the out-patient department of Periodontics in A B Shetty Memorial Institute of Dental Sciences.
Patients and Methods: Seventy-five patients in the age group of 18-60 years were selected and grouped based on the gingival index (Loe and Sillness) and their clinical attachment levels into healthy, gingivitis and periodontitis groups. Leptin and IL-6 levels were estimated within gingiva and the plasma of each subject using an enzyme-linked immunosorbent assay kit. The results of this study were tabulated and subjected to statistical analysis. Mean and the standard deviation were calculated using analysis of variance Fisher's F-test and then the results were subjected to Tukey's Honest significance difference method for multiple comparison among the three groups. Correlation among the three groups was estimated using Pearson's correlation analysis.
Results: Results showed a statistically significant decrease in the concentration of gingival leptin and a statistically significant increase in the concentration of plasma leptin as the gingival disease progressed.
Conclusion: It was concluded that as the gingival disease progressed, the gingival leptin concentration decreased, whereas the plasma leptin concentration increased, indicating a possible correlation between leptin concentration in the gingiva and the risk of developing systemic disease like the cardiovascular disease.

Keywords: Gingival leptin, interleukin 6, healthy gingiva, gingivitis, periodontitis

How to cite this article:
Gangadhar V, Ramesh A, Thomas B. Correlation between leptin and the health of the gingiva: A predictor of medical risk. Indian J Dent Res 2011;22:537-41

How to cite this URL:
Gangadhar V, Ramesh A, Thomas B. Correlation between leptin and the health of the gingiva: A predictor of medical risk. Indian J Dent Res [serial online] 2011 [cited 2019 Sep 20];22:537-41. Available from: http://www.ijdr.in/text.asp?2011/22/4/537/90292
Leptin is a 16 kDa adipocyte-derived circulating protein. [1],[2] It controls adipose tissue weight by stimulating lipid metabolism in the organism. [3] High leptin concentration in an obese individual may reflect the resistance to the effect of the hormones, [4],[5] and also elevated plasma leptin concentration has been suggested as a risk factor for the cardiovascular diseases. [6] Sieminska et al. in 2002 studied whether there was any connection between serum leptin and the presence and extent of coronary arteriosclerosis. Serum levels of leptin were significantly higher in the group with coronary artery disease (P < 0.01). They concluded that leptin probably is one of the many factors involved in the pathogenesis of complication of obesity related atherosclerosis, hypertension and diabetes. [7]

Leptin may also play a role in mediating the inflammatory response; increase in leptin levels has been implicated as a host defense mechanism during sepsis. Marruna and Rosicka in 1998 studied the changes of circulating leptin in relation to a set of proinflammatory cytokines, soluble cytokine receptor of interleukin (IL)-2, acute phase proteins (APP) and body mass index (BMI). Plasma levels of leptin, tumor necrosis factor-α (TNF-α), IL-1β and IL-6 [enzyme-linked immunosorbent assay (ELISA) analysis] were estimated. Blood samples were collected during first 5 days of septic period (1st group) or before operation and +24, +48, and +72 hours after surgery (2nd and 3rd groups). Results demonstrated statistically significant elevation of plasma leptin concentration in septic group compared with healthy subjects and postoperative levels. Among the cytokines, there was significant correlation between TNF-α and leptin and between IL-6 and leptin. It was concluded that during infections, leptin is released in response to stress and can act as an acute phase reactant.[8]

Leptin is present within healthy gingiva and its concentration declines with the increase in severity of the gingival inflammation and periodontal pocket formation. [9] If this decline in the concentration of leptin within the gingiva is due to its release into the plasma, thus increasing the plasma leptin concentration, it could increase the risk for the development of cardiovascular diseases. The aims of the present study were:

  • to estimate the concentration of leptin and IL-6 within healthy and diseased gingiva and
  • to correlate gingival leptin concentration with the plasma leptin concentration as the gingival disease progressed.



   Patients and Methods Top


This study was conducted in the Department of Periodontics, A B Shetty Memorial Institute of Dental Sciences, Mangalore. A total of 75 moderately built patients of age between 18 and 60 years were selected based on the following inclusion criteria:

  • Patients having teeth indicated for extraction for orthodontic treatment, dental caries or periodontitis.
  • Teeth were included and grouped based on the gingival index by Loe and Sillness [10] and the clinical attachment loss [11] into three groups [Table 1].
  • Table 1: Selection and grouping of the teeth

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Exclusion criteria

  • Patient having any systemic disease.
  • Patient taking any antibiotic/anti inflammatory drugs for the past 6 months.
  • Patients with teeth which were partially erupted or impacted.


The results of this study were tabulated and subjected to statistical analysis. Mean and standard deviation were calculated for quantitative data analysis. Mean and the standard deviation were calculated using analysis of variance (ANOVA) Fisher's F-test and then the results were subjected to Tukey's Honest significance difference (HSD) method for multiple comparison among the three groups. Pearson's correlation analysis was used to correlate the values of gingival leptin and IL-6 and serum leptin and IL-6 among the three groups.

Procedure

Seventy-five subjects were selected, a detail case history was recorded and the subjects were grouped into three, based on the above mentioned criteria.

Blood samples were collected from the patients belonging to each group. Two milliliters of the collected blood was transferred to a vial and centrifuged in a centrifugator for 10 minutes.

Gingival index (Loe and Silness) [10] was used to assess the severity of the gingival status. It was recorded on four gingival surfaces of the selected tooth, i.e. the distofacial papilla, facial margin, mesiofacial papilla and the entire lingual gingival margin. A periodontal probe was used to asses the bleeding potential of the tissues.

Each of the four gingival units was assessed according to the following criteria:

0- Normal gingiva

1- Mild inflammation, slight change in color, slight edema, no bleeding on probing

2- Moderate inflammation, moderate glazing, redness and edema, bleeding on probing

3- Severe inflammation, marked redness, edema, ulceration and tendency to spontaneous bleeding

Totaling the score around each tooth and dividing by four gives the gingival index for the tooth.

Mean clinical attachment level was determined by measuring the distance from cemento enamel junction CEJ (a stationary point of reference) to the most apical extent of the periodontal probe penetration [11] on the teeth to be extracted, prior to biopsy.

The selected gingival site was isolated and anesthetized. The gingival tissue was carefully removed with a scalpel. The excised tissue was frozen and stored. Tissue samples were solubilized by grinding in the phosphate buffered saline and were subjected to biochemical analysis. Total protein concentration was estimated by using biuret method (Instruction manual: Biuret method for total protein estimation, Nicholas Piramal India Limited). [12] Concentrations of leptin and IL-6 were estimated using ELISA kit (leptin sandwich ELISA, DRG, International Inc., USA, and Biotrack IL 6 ESA system, Amersham Biosciences Germany). [13]


   Results Top


The mean gingival leptin concentration was 377.92 ± 31.15 pg/mg of protein in the healthy group, 321.96 ± 15.37 pg/mg of protein in gingivitis group and 212.52 ± 28.29 pg/mg of protein in the periodontitis group. On the other hand, serum leptin concentration was 4352 ± 12.26 pg/mg, 7610 ± 4352 pg/mg and 8129 ± 7610 pg/mg in healthy, gingivitis and periodontitis groups, respectively [Table 2]. The intercomparison among the three groups was found to be statistically very highly significant (P = 0.001) [Table 2]. The results indicated that the gingival leptin concentrations were found to decrease whereas serum leptin concentrations were found to increase as the gingival disease progressed [Graph 1] and [Graph 2].
Table 2: Intercomparison of mean leptin concentrations in gingiva and serum

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Multiple comparisons among the three groups showed that the mean difference in the leptin concentration was 55.9600 and -3258 in the gingiva and the serum, respectively, while comparing healthy and gingivitis groups; 165.400 and -3777 in gingiva and serum, respectively, while comparing healthy and periodontitis groups; and finally, 109.4400 and -519.600 in gingiva and serum, respectively, while comparing gingivitis and periodontitis group. The multiple comparisons among all the groups were found to be statistically very highly significant (P = 0.001) [Table 3].
Table 3: Multiple comparison of leptin within gingiva and serum among the three groups

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The mean gingival IL-6 concentration was 5.84 ± 0.19 pg/mg of protein in the healthy group, 5.24 ± 5.84 pg/mg of protein in gingivitis group and 12.26 ± 5.24 pg/mg of protein in the periodontitis group. On the other hand, in the serum, the IL-6 concentration was 3.43 ± 0.34 pg/mg, 3.33 ± 0.15 pg/mg and 4.26 ± 0.19 pg/mg in healthy, gingivitis and periodontitis groups, respectively. The intercomparison among the three groups was found to be statistically very highly significant (P = 0.001) [Table 4]. The gingival IL-6 concentrations were found to increase in both gingiva as well as serum as the gingival disease progressed [Graph 3] and [Graph 4].
Table 4: Intercomparison of mean IL-6 concentration in gingiva and serum

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Multiple comparisons among the three groups showed that the mean difference in the IL-6 concentration was 0.5960 and 0.1000 in the gingiva and the serum, respectively, while comparing healthy and gingivitis groups; -6.4160 and -0.8320 in gingiva and serum, respectively, while comparing healthy and periodontitis groups; and finally, -7.0120 and -0.9320 in gingiva and serum, respectively, while comparing gingivitis and periodontitis groups. The multiple comparisons among all the groups were statistically very highly significant (P = 0.001) except for the mean difference in the serum IL-6 concentration, while comparing healthy and gingivitis groups (P = 0.303) [Table 5].
Table 5: Multiple comparison of IL-6 within gingiva and serum among the three groups

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There was a positive correlation between gingival and serum leptin as well as gingival and serum IL-6 concentrations of 0.338 and 0.244, respectively, in the healthy group. Similarly, there was a positive correlation between gingival and serum leptin as well as IL-6 concentration of 0.013 and 0.114, respectively, in the periodontitis group. On the other hand, there was a negative correlation between gingival and serum leptin as well as IL-6 concentration of -0.373 and -0.266, respectively, in gingivitis group. However, the correlations between gingival and serum concentrations of leptin and IL-6 among the three groups were not statistically significant [Table 6].
Table 6: Correlation between gingival and serum leptin and gingival and serum IL-6 within each of the three groups

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   Discussion Top


The discovery of leptin had long been anticipated before its actual isolation. [14] Leptin is a hormone that is secreted in the blood in varying quantities by adipocytes and controls the adipose tissue weight by stimulating lipid metabolism by the organism. [15] Adipocytes in the obese people produce a large quantity of biologically active molecules such as leptin, and high leptin concentration in blood has been suggested as a risk factor for the cardiovascular diseases. [16] This is probably the first study to report the concentration of leptin within the gingiva of healthy, gingivitis and periodontitis patients and its correlation with the serum leptin concentration.

Mean gingival IL-6 concentrations were also estimated in the gingiva of healthy, gingivitis and periodontitis groups and this was correlated with the serum IL-6 concentrations. The leptin receptor is homologous to the gp 130 family of receptors, the signal transducing subunit of the IL-6 type cytokine receptors, supporting the hypotheses that leptin and IL-6 may both have roles in the inflammatory process. [17] Although IL-6 and leptin are both hypersecreted during sepsis in humans, there was a reported negative correlation between leptin concentration and patient survival, a situation similar to that within the gingiva during progression of periodontal diseases. [9]

The results obtained in the present study are in accordance with the study conducted by Johnson and Serio in 2001 and Mc Gee and Tucci in 1998. In these studies, leptin, IL-6 and vascular endothelial growth factor (VGEF) were estimated within the healthy and diseased gingival. [18]

In addition to the estimation of leptin within the healthy and the diseased gingiva, in the present study, leptin was also estimated in the plasma of the subjects in the healthy, gingivitis and periodontitis groups. In this study, a decrease in the gingival leptin concentration was found as the disease progressed, along with an increase in the plasma leptin concentration. The mechanism underlying a reduction in leptin concentration during the progression of gingival inflammation may probably be due to its release into the serum, as shown in this study. However, the correlation between the gingival and the serum leptin concentrations was not found to be statistically significant; this discrepancy might be due to the small sample size taken in this study.

Elevated plasma leptin concentrations have been suggested as a risk factor for disorders like cardiovascular disease and diabetes mellitus. This study showed an increase in the plasma leptin concentration and a decrease in the gingival leptin concentration as the gingival disease progressed, suggesting a possible link; however, this correlation was not found to be statistically significant. Since leptin is produced by adipocytes, the presence of leptin within the gingiva is somewhat puzzling. There is currently no evidence that the resident gingival cells such as the fibroblasts or the epithelial cells produce leptin. Since the source of leptin within the gingiva is unknown, its presence could be due to the entrapment within the gingiva by diffusion from the microvasculature. An additional study of this possibility is required.


   Conclusion Top


Within the limitations of the present study, it can be concluded that leptin is present within the gingiva and its concentration decreases as the gingival inflammation increases. Leptin was also found to be present in the plasma and its concentration was found to increase as the gingival disease progressed. With the prior knowledge that increased plasma leptin concentration is a risk factor for the development of diseases like cardiovascular disease, the associated increase in the leptin concentration in the plasma in relation to the increase in the gingival inflammation indicates that gingival inflammation may increase the risk of developing systemic diseases.


   Acknowledgments Top


I express my sincere thanks to Dr. Suchetha Shetty for her immense knowledge and her constant strive for perfection to help conduct biochemical laboratory procedures. I would also like to extend my heartfelt thanks to Dr. Mohammed Faizuddin, Head of the department of Periodontics, M R Ambedkar Dental College and Hospital, for the valuable advice, suggestion and guidance for publishing my article.



 
   References Top

1.Frederich RC, Hamann A, Anderson S, Lollman B, Lowell BB, Flier JS. Leptin levels reflect body lipid content in mice: evidence for diet- induced resistance to leptin action. Nat Med 1995;1:1311-4.  Back to cited text no. 1
    
2.Mac Donald OA, Hwang CS, Fan H, Lane MD. Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. Proc Natl Acad Sci U.S.A. 1995;92:9034-7.  Back to cited text no. 2
    
3.Montani JP,Antic V, Yang Z, Dulloo A. Pathways from obesity to hypertension: from the perspective of a vicious triangle. Int J Obes Relat Metab Disord 2002Sep. 26 Suppl 2: S28-38.  Back to cited text no. 3
    
4.Hamilton BS, Paglia D, Kwan AY, Deitel M. Increased obese mRNA expression in developmental fat cells from massively obese humans. Nat Med 1995;1:953-56.  Back to cited text no. 4
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5.Lonnqvist F, Arner P, Nordfors L, Schalling M. Over expression of the obese (0b) gene in adipose tissue of human obese subjects. Nature Med 1995;1:950-2.  Back to cited text no. 5
    
6.Levya F, Godsland IF, Ghatei M. Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk. Arterioscler Throm Vasc Biol 1998;18:928-33.  Back to cited text no. 6
    
7.Sieminska L. Hyperleptinemia and cardiovascular disease. Endocr Abstr 2002;4:43.  Back to cited text no. 7
    
8.Maruna P, Rosicka M. Leptin as a new inflammatory mediator. The relation to cytokines, acute phase proteins and body mass index. FASEB J 1998;12:57-65.  Back to cited text no. 8
    
9.Johnson RB, Serio FG. Leptin within healthy and diseased human gingival. J Periodontol 2001;72:1254-7.  Back to cited text no. 9
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10.Loe H. The gingival index, plaque index and the retention index. J Periodontol 1967;38:610.   Back to cited text no. 10
    
11.Armitage GC. Periodontal disease: Diagnosis Ann Periodontol 1996;1:37-215.  Back to cited text no. 11
    
12.Instruction manual: Biuret method for total protein estimation, Nicholas Piramal India Limited.  Back to cited text no. 12
    
13.Instruction manual: Leptin (sandwich) ELISA, DRG Instruments GmbH, Germany.  Back to cited text no. 13
    
14.Wang Y, Kuropatwinski KK, White DW, Hawley TS, Hawley RG, Tartaglia LA, Baumann M. Leptin receptor action in the hepatic cell. J Biol Chem 1997;277:16216-23.   Back to cited text no. 14
    
15.Pankov Iu A. Leptin - a peptide hormone from adipocyte. Sensation of the 23rd FEBS meeting. Bioorg Khim 1996;22:228-33.  Back to cited text no. 15
    
16.Ogawa Y, Masuzaki H, Isse N, Okazaki T, Mori K, Shigemoto M, et al. Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese zucker falty (fa/fa) rat. J Clin Invest 1995;96:1647-52.  Back to cited text no. 16
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17.Guillot JL, Pollock SM, Johnson RB. Gingival interleukin 6 concentration following phase I therapy. J Periodontol 1995;66:667-72.  Back to cited text no. 17
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18.Mc Gee JM, Tucci MA. The relationship between concentration of proinflammatory cytokines within gingiva and the adjacent sulcular depth. J Periodontol 1998;69:865-71.  Back to cited text no. 18
    

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Correspondence Address:
Vidhya Gangadhar
Department of Periodontics, M R Ambedkar Dental College, Bangalore
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.90292

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

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