Advertisement

Clinical Oral Investigations

, Volume 23, Issue 2, pp 937–946 | Cite as

Characterization of a diet-induced obesity rat model for periodontal research

  • Anna Damanaki
  • Marjan Nokhbehsaim
  • Kanishka Hiththetiya
  • Svenja Memmert
  • Jinlong Gao
  • Ky-Anh Nguyen
  • Werner Götz
  • Andreas Jäger
  • Gerhard Wahl
  • James DeschnerEmail author
Original Article
  • 155 Downloads

Abstract

Objectives

Obesity is associated with periodontitis, but the mechanisms underlying this association have yet to be unraveled. The present investigation was to evaluate a common rat model, in which obesity is induced by high-fat, high-sucrose diet (HFSD), for its applicability in periodontal research.

Materials and methods

Ten male Wistar rats were fed a 3-month HFSD along with a matching control group. Afterwards, the body weight, adipocyte morphology, leptin and adiponectin levels in adipose tissue, gingiva, and serum as well as the serum levels of triglyceride, cholesterol, and glucose were analyzed. For statistical analyses, parametric and non-parametric tests were applied (p < 0.05).

Results

Body weight was significantly higher in the HFSD group after dieting as compared to control. HFSD caused a significant increase in serum triglyceride, low-density lipoprotein cholesterol, and leptin levels and a significant decrease in high-density lipoprotein cholesterol. Furthermore, adipose tissue from HFSD rats exhibited significantly larger adipocytes, displayed a significant upregulation of leptin and, surprisingly, elevated adiponectin levels, which is in contrast to chronic obesity in humans. Although leptin and adiponectin were also observed in gingival biopsies, no obvious differences between the groups were found.

Conclusions

Although this rat diet-induced obesity model is characterized by changes typical of obesity, it also has limitations, which have to be considered when data, especially with regard to adipokines, are extrapolated to humans.

Clinical relevance

The rodent diet-induced obesity model may be useful for unraveling pathomechanisms underlying the association between obesity and periodontal destruction but conclusions have to be drawn with caution.

Keywords

Obesity Animal model Adipokine Gingiva Adipose tissue Serum 

Notes

Acknowledgements

The authors would like to thank Prof. Heiko Spallek, Prof. Glen Kristiansen, Dr. Anja Winkler, Ms. Ramona Menden, and Ms. Silke van Dyck for their valuable support.

Funding

This study was supported by the Medical Faculty of the University of Bonn, the German Research Foundation (DFG/ KFO208/TP4/TP9), and the University of Sydney.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in this study were in accordance with the ethical standards of the University of Bonn (Az 87-51.04.2010.A394).

References

  1. 1.
    Fruh SM (2017) Obesity: risk factors, complications, and strategies for sustainable long-term weight management. J Am Assoc Nurse Pract 29:S3–S14Google Scholar
  2. 2.
    Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NME, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DFJ, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SEAH, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KMV, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJC, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang XR, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJL, Gakidou E (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the global burden of disease study 2013. Lancet 384:766–781CrossRefGoogle Scholar
  3. 3.
    Martens L, De Smet S, Yusof MY, Rajasekharan S (2017) Association between overweight/obesity and periodontal disease in children and adolescents: a systematic review and meta-analysis. Eur Arch Paediatr Dent 18:69–82CrossRefGoogle Scholar
  4. 4.
    Moura-Grec PG, Marsicano JA, Carvalho CA, Sales-Peres SH (2014) Obesity and periodontitis: systematic review and meta-analysis. Cien Saude Colet 19:1763–1772CrossRefGoogle Scholar
  5. 5.
    Suvan J, D'Aiuto F, Moles DR, Petrie A, Donos N (2011) Association between overweight/obesity and periodontitis in adults. A systematic review. Obes Rev 12:e381–e404CrossRefGoogle Scholar
  6. 6.
    Perlstein MI, Bissada NF (1977) Influence of obesity and hypertension on the severity of periodontitis in rats. Oral Surg Oral Med Oral Pathol 43:707–719CrossRefGoogle Scholar
  7. 7.
    Saito T, Shimazaki Y, Sakamoto M (1998) Obesity and periodontitis. N Engl J Med 339:482–483CrossRefGoogle Scholar
  8. 8.
    Nascimento GG, Leite FR, Do LG et al (2015) Is weight gain associated with the incidence of periodontitis? A systematic review and meta-analysis. J Clin Periodontol 42:495–505CrossRefGoogle Scholar
  9. 9.
    Amar S, Leeman S (2013) Periodontal innate immune mechanisms relevant to obesity. Mol Oral Microbiol 28:331–341CrossRefGoogle Scholar
  10. 10.
    Zelkha SA, Freilich RW, Amar S (2010) Periodontal innate immune mechanisms relevant to atherosclerosis and obesity. Periodontol 54:207–221CrossRefGoogle Scholar
  11. 11.
    Amar S, Zhou Q, Shaik-Dasthagirisaheb Y, Leeman S (2007) Diet-induced obesity in mice causes changes in immune responses and bone loss manifested by bacterial challenge. Proc Natl Acad Sci U S A 104:20466–20471CrossRefGoogle Scholar
  12. 12.
    Adamczak M, Wiecek A (2013) The adipose tissue as an endocrine organ. Semin Nephrol 33:2–13CrossRefGoogle Scholar
  13. 13.
    Krysiak R, Handzlik-Orlik G, Okopien B (2012) The role of adipokines in connective tissue diseases. Eur J Nutr 51:513–528CrossRefGoogle Scholar
  14. 14.
    Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295CrossRefGoogle Scholar
  15. 15.
    Carbone F, La Rocca C, Matarese G (2012) Immunological functions of leptin and adiponectin. Biochimie 94:2082–2088CrossRefGoogle Scholar
  16. 16.
    La Cava A (2012) Proinflammatory activities of leptin in non-autoimmune conditions. Inflamm Allergy Drug Targets 11:298–302CrossRefGoogle Scholar
  17. 17.
    Paz-Filho G, Mastronardi C, Franco CB, Wang KB, Wong ML, Licinio J (2012) Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arq Bras Endocrinol Metabol 56:597–607CrossRefGoogle Scholar
  18. 18.
    Procaccini C, Jirillo E, Matarese G (2012) Leptin as an immunomodulator. Mol Asp Med 33:35–45CrossRefGoogle Scholar
  19. 19.
    Zhou Y, Rui L (2013) Leptin signaling and leptin resistance. Front Med 7:207–222CrossRefGoogle Scholar
  20. 20.
    Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS, Caprio S (2004) Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 350:2362–2374CrossRefGoogle Scholar
  21. 21.
    Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599CrossRefGoogle Scholar
  22. 22.
    Fantuzzi G (2013) Adiponectin in inflammatory and immune-mediated diseases. Cytokine 64:1–10CrossRefGoogle Scholar
  23. 23.
    Turer AT, Scherer PE (2012) Adiponectin: mechanistic insights and clinical implications. Diabetologia 55:2319–2326CrossRefGoogle Scholar
  24. 24.
    Villarreal-Molina MT, Antuna-Puente B (2012) Adiponectin: anti-inflammatory and cardioprotective effects. Biochimie 94:2143–2149CrossRefGoogle Scholar
  25. 25.
    Fiaschi T, Magherini F, Gamberi T, Modesti PA, Modesti A (2014) Adiponectin as a tissue regenerating hormone: more than a metabolic function. Cell Mol Life Sci 71:1917–1925CrossRefGoogle Scholar
  26. 26.
    Cheng KK, Lam KS, Wang B, Xu A (2014) Signaling mechanisms underlying the insulin-sensitizing effects of adiponectin. Best Pract Res Clin Endocrinol Metab 28:3–13CrossRefGoogle Scholar
  27. 27.
    Liu M, Liu F (2014) Regulation of adiponectin multimerization, signaling and function. Best Pract Res Clin Endocrinol Metab 28:25–31CrossRefGoogle Scholar
  28. 28.
    Yamauchi T, Iwabu M, Okada-Iwabu M, Kadowaki T (2014) Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab 28:15–23CrossRefGoogle Scholar
  29. 29.
    Zhang L, Meng S, Tu Q, Yu L, Tang Y, Dard MM, Kim SH, Valverde P, Zhou X, Chen J (2014) Adiponectin ameliorates experimental periodontitis in diet-induced obesity mice. PLoS One 9:e97824CrossRefGoogle Scholar
  30. 30.
    Rosini TC, Silva AS (1992) Moraes Cd (2012) Diet-induced obesity: rodent model for the study of obesity-related disorders. Rev Assoc Med Bras 58:383–387Google Scholar
  31. 31.
    Kuraji R, Fujita M, Ito H, Hashimoto S, Numabe Y (2017) Effects of experimental periodontitis on the metabolic system in rats with diet-induced obesity (DIO): an analysis of serum biochemical parameters. Odontology 106:162–170.  https://doi.org/10.1007/s10266-017-0322-5 CrossRefGoogle Scholar
  32. 32.
    Zuza EP, Garcia VG, Theodoro LH, Ervolino E, Favero LFV, Longo M, Ribeiro FS, Martins AT, Spolidorio LC, Zuanon JAS, de Toledo BEC, Pires JR (2017) Influence of obesity on experimental periodontitis in rats: histopathological, histometric and immunohistochemical study. Clin Oral Investig 22:1197–1208.  https://doi.org/10.1007/s00784-017-2207-y CrossRefGoogle Scholar
  33. 33.
    Virto L, Cano P, Jiménez-Ortega V, Fernández-Mateos P, González J, Esquifino AI, Sanz M (2018) Obesity and periodontitis. Obesity and periodontitis: an experimental study to evaluate periodontal and systemic effects of comorbidity. J Periodontol 89:176–185Google Scholar
  34. 34.
    Cavagni J, de Macedo IC, Gaio EJ, Souza A, de Molon RS, Cirelli JA, Hoefel AL, Kucharski LC, Torres ILS, Rösing CK (2016) Obesity and hyperlipidemia modulate alveolar bone loss in Wistar rats. J Periodontol 87:e9–e17CrossRefGoogle Scholar
  35. 35.
    Deschner J, Eick S, Damanaki A, Nokhbehsaim M (2014) The role of adipokines in periodontal infection and healing. Mol Oral Microbiol 29:258–269CrossRefGoogle Scholar
  36. 36.
    Nokhbehsaim M, Eick S, Nogueira AV et al (2013) Stimulation of MMP-1 and CCL2 by NAMPT in PDL cells. Mediat Inflamm 2013:437123Google Scholar
  37. 37.
    Kraus D, Winter J, Jepsen S, Jäger A, Meyer R, Deschner J (2012) Interactions of adiponectin and lipopolysaccharide from Porphyromonas gingivalis on human oral epithelial cells. PLoS One 7:e30716CrossRefGoogle Scholar
  38. 38.
    Nokhbehsaim M, Keser S, Nogueira AV et al (2014) Beneficial effects of adiponectin on periodontal ligament cells under normal and regenerative conditions. J Diabetes Res 2014:796565CrossRefGoogle Scholar
  39. 39.
    Nokhbehsaim M, Keser S, Nogueira AV et al (2014) Leptin effects on the regenerative capacity of human periodontal cells. Int J Endocrinol 2014:180304CrossRefGoogle Scholar
  40. 40.
    Kim SJ (2010) Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-alpha in monocyte-derived macrophages. J Periodontal Implant Sci 40:119–124CrossRefGoogle Scholar
  41. 41.
    Kamio N, Akifusa S, Yamaguchi N, Nonaka K, Yamashita Y (2009) Anti-inflammatory activity of a globular adiponectin function on RAW 264 cells stimulated by lipopolysaccharide from Aggregatibacter actinomycetemcomitans. FEMS Immunol Med Microbiol 56:241–247CrossRefGoogle Scholar
  42. 42.
    Zimmermann GS, Bastos MF, Dias Gonçalves TE, Chambrone L, Duarte PM (2013) Local and circulating levels of adipocytokines in obese and normal weight individuals with chronic periodontitis. J Periodontol 84:624–633CrossRefGoogle Scholar
  43. 43.
    Kardeşler L, Buduneli N, Cetinkalp S, Kinane DF (2010) Adipokines and inflammatory mediators after initial periodontal treatment in patients with type 2 diabetes and chronic periodontitis. J Periodontol 81:24–33CrossRefGoogle Scholar
  44. 44.
    Shimada Y, Komatsu Y, Ikezawa-Suzuki I, Tai H, Sugita N, Yoshie H (2010) The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein. J Periodontol 81:1118–1123CrossRefGoogle Scholar
  45. 45.
    Damanaki A, Nokhbehsaim M, Eick S, Götz W, Winter J, Wahl G, Jäger A, Jepsen S, Deschner J (2014) Regulation of NAMPT in human gingival fibroblasts and biopsies. Mediat Inflamm 2014:912821, 1, 10Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Anna Damanaki
    • 1
  • Marjan Nokhbehsaim
    • 1
  • Kanishka Hiththetiya
    • 2
  • Svenja Memmert
    • 1
    • 3
  • Jinlong Gao
    • 4
  • Ky-Anh Nguyen
    • 4
  • Werner Götz
    • 3
  • Andreas Jäger
    • 3
  • Gerhard Wahl
    • 5
  • James Deschner
    • 1
    • 6
    • 7
    Email author
  1. 1.Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial MedicineUniversity of BonnBonnGermany
  2. 2.Department of PathologyUniversity of BonnBonnGermany
  3. 3.Department of Orthodontics, Center of Dento-Maxillo-Facial MedicineUniversity of BonnBonnGermany
  4. 4.Westmead Institute for Medical Research and Faculty of DentistryUniversity of SydneySydneyAustralia
  5. 5.Department of Oral Surgery, Center of Dento-Maxillo-Facial MedicineUniversity of BonnBonnGermany
  6. 6.Noel Martin Visiting Chair, Faculty of DentistryUniversity of SydneySydneyAustralia
  7. 7.Department of Periodontology and Operative DentistryUniversity Medical Center, Johannes Gutenberg UniversityMainzAustralia

Personalised recommendations