Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Effect of C60 fullerene nanoparticles on the diet-induced obesity in rats

ABSTRACT

Background

Obesity is a growing global health problem. Since increased oxidative stress is one of the key pathological mechanisms underpinning overweight and strongly correlates with progression of obesity-related complications we hypothesized that C60 fullerene nanoparticles, due to their strong antioxidant capacity, could be the promising therapeutic agent in the treatment of this disease. Here we investigated whether the C60 fullerenes can alleviate diet-induced obesity (DIO) and metabolic impairments associated with it.

Methods

To determine the effect of C60 fullerenes on some nutritional and metabolic parameters, rats were fed either a normal diet (6.7% fat, 15.27 kJ·g−1) or a high-fat diet (38.8% fat, 28.71 kJ·g−1) for 70 days and were simultaneously treated per os with pristine C60 fullerene aqueous solution (C60FAS; 0.3 mg·kg−1 every other day) since the 28th day from the start of the experiment.

Results

Rats fed with high fat diet had significantly increased body mass index (BMI), levels of insulin, glucose, glycosilated hemoglobin (HbA1c) and serum pro-inflammatory cytokines compared with control rats fed with low-fat chow. C60 fullerenes normalized the metabolic parameters and partially reduced BMI in DIO animals. Pro-inflammatory cytokines (IL-1b, IL-12, INFγ) were also decreased in serum of DIO rats treated with C60 fullerenes while anti-inflammatory cytokines (IL-4, IL-10) were at the control levels. High fat diet caused the increased level of oxidative stress products, and this was accompanied by decreased activity both the superoxide dismutase and catalase, whereas the administration of C60 fullerenes markedly decreased level of oxidative stress and enhanced antioxidant enzyme activities.

Conclusion

These data indicate that water-soluble pristine C60 fullerenes reduce chronic inflammation, restore glucose homeostasis as well as positively affects on prooxidant-antioxidant homeostasis. C60 fullerenes could be represented as a promising therapeutic agent in the treatment of obesity and its related complications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. World Health Organization, WHO, Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation (WHO Technical Report Series 894), http://www.who.int/nutrition/publications/obesity/WHO_TRS_894/en/, (accessed 10 Feb 2016).

  2. Malnick SD, Knobler H. The medical complications of obesity. QJM. 2006;99:565–79.

    Article  CAS  Google Scholar 

  3. Segula D. Complications of obesity in adults: A short review of the literature. Malawi Med J. 2014;26:20–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Qatanani M, Lazar MA. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev. 2007;21:1443–55.

    Article  CAS  Google Scholar 

  5. Golay A, Ybarra J. Link between obesity and type 2 diabetes. Best Pract Res Clin Endocrinol Metab. 2005;19:649–63.

    Article  CAS  Google Scholar 

  6. Novelli ELB, Fernandes A, Campos K, Diniz Y, Almeida J, Ribas BO. The adverse effects of a high-energy dense diet on cardiac tissue. Journal of Nutritional and Environmental Medicine. 2002;12:287–90.

    Article  CAS  Google Scholar 

  7. Bianchini F, Kaaks R, Vainiuo H. Overweight, obesity and cancer risk. Lancet Oncology. 2002;3:565–74.

    Article  Google Scholar 

  8. Mafort TT, Rufino R, Costa CH, Lopes AJ. Obesity: systemic and pulmonary complications, biochemical abnormalities, and impairment of lung function. Multidiscip. Resp. Med. 2016;11:28.

    Article  Google Scholar 

  9. Marseglia L, Manti S, D’Angelo G, Nicotera A, Parisi E, Di Rosa G, et al. Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci. 2014;16:378–400.

    Article  Google Scholar 

  10. Serra D, Mera P, Malandrino MI, Mir JF, Herrero L. Mitochondrial fatty acid oxidation in obesity. Antioxid Redox Signal. 2013;19:269–84.

    Article  CAS  Google Scholar 

  11. Tiganis T. Reactive oxygen species and insulin resistance: the good, the bad and the ugly. Trends Pharmacol Sci. 2011;32:82–9.

    Article  CAS  Google Scholar 

  12. Sakai K, Matsumoto K, Nishikawa T, Suefuji M, Nakamaru K, Hirashimaet Y, et al. Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells. Biochem Biophys Res Commun. 2003;300:216–22.

    Article  CAS  Google Scholar 

  13. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114:1752–61.

    Article  CAS  Google Scholar 

  14. Rocca A, Moscato S, Ronca F, Nitti S, Mattoli V, Giorgi M, et al. Pilot in vivo investigation of cerium oxide nanoparticles as a novel anti-obesity pharmaceutical formulation. Nanomedicine. 2015;11:1725–34.

    Article  CAS  Google Scholar 

  15. Bogdanović G, Djordjević A. Carbon nanomaterials: Biologically active fullerene derivatives. Srp Arh Celok Lek. 2016;144:222–31.

    Article  Google Scholar 

  16. Prylutskyy YI, Yashchuk VM, Kushnir KM, et al. Biophysical studies of fullerene-based composite for bio-nanotechnology. Mater. Sci. Engineer. C. 2003;23:109–11.

    Article  Google Scholar 

  17. Prylutskyy YI, Petrenko VI, Ivankov OI, Golub AA, Kudrenko VA, Prylutska SV, et al. On the origin of C60 fullerene solubility in aqueous solution. Langmuir. 2014;30:3967–70.

    Article  CAS  Google Scholar 

  18. Ritter U, Prylutskyy YI, Evstigneev MP, Davidenko NA, Cherepanov VV, Senenko AI, et al. Structural features of highly stable reproducible C60 fullerene aqueous colloid solution probed by various techniques. Fullerenes, Nanotubes, Carbon Nanostruct. 2015;23:530–34.

    Article  CAS  Google Scholar 

  19. Foley S, Crowley C, Smaihi M, Bonfils C, Erlanger BF, Seta P, et al. Cellular localisation of a water-soluble fullerene derivative. Biochem Biophys Res Commun. 2002;294:116–9.

    Article  CAS  Google Scholar 

  20. Schuetze C, Ritter U, Scharff P, Bychko A, Prylutska S, Rybalchenko V, et al. Interaction of N-fluorescein-5-isothiocyanate pyrrolidine-C60 compound with a model bimolecular lipid membrane. Mater. Sci. Engineer. C. 2011;31:1148–50.

    Article  CAS  Google Scholar 

  21. Franskevych D, Palyvoda K, Petukhov D, Prylutska S, Grynyuk I, Schuetze C, et al. Fullerene C60 penetration into leukemic cells and its photoinduced cytotoxic effects. Nanoscale Res Lett. 2017;12:40.

    Article  CAS  Google Scholar 

  22. Wang IC, Tai LA, Lee DD, Kanakamma PP, Shen CK, Luh TY, et al. C(60) and water-soluble fullerene derivatives as antioxidants against radical-initiated lipid peroxidation. J Med Chem. 1999;42:4614–20.

    Article  CAS  Google Scholar 

  23. Burlaka АP, Sidorik ЕP, Prylutska SV, Маtyshevska ОP, Golub АА, Prylutskyy YI, et al. Catalytic system of the reactive oxygen species on the C60 fullerene basis. Exp Oncol. 2004;26:326–27.

    CAS  PubMed  Google Scholar 

  24. Gharbi N, Pressac M, Hadchouel M, Szwarc H, Wilson SR, Moussa F. [60]fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett. 2005;5:2578–85.

    Article  CAS  Google Scholar 

  25. Youle RJ, Karbowski M. Opinion: mitochondrial fission in apoptosis. Nature Rev. Mol. Cell. Biol. 2005;6:657–63.

    Article  CAS  Google Scholar 

  26. Sayes CM, Fortner JD, Guo W, Lyon D, Boyd AM, Ausman KD, et al. The differential cytotoxicity of water-soluble fullerenes. Nano Lett. 2004;4:1881–87.

    Article  CAS  Google Scholar 

  27. Prylutska SV, Matyshevska OP, Golub AА, Prylutskyy YI, Potebnya GP, Ritter U, Scharff P. Study of С60 fullerenes and С60-containing composites cytotoxicity in vitro. Mater. Sci. Engineer. C. 2007;27:1121–4.

    Article  CAS  Google Scholar 

  28. Prylutska SV, Grynyuk II, Grebinyk SM, Matyshevska OP, Prylutskyy YI, Ritter U, et al. Comparative study of biological action of fullerenes C60 and carbon nanotubes in thymus cells. Mat.-wiss. u. Werkstofftech. 2009;40:238–41.

    Article  CAS  Google Scholar 

  29. Tolkachov M, Sokolova V, Korolovych V, Prylutskyy Yu, Epple M, Ritter U, et al. Study of biocompatibility effect of nanocarbon particles on various cell types in vitro. Mat.-wiss. u. Werkstofftech. 2016;47:216–21.

    Article  CAS  Google Scholar 

  30. Halenova TI, Vareniuk IM, Roslova NM, Dzerzhynsky ME, Savchuk OM, Ostapchenko LI, et al. Hepatoprotective effect of orally applied water-soluble pristine C60 fullerene against CCl4-induced acute liver injury in rats. RSC Adv. 2016;6:100046–55.

    Article  CAS  Google Scholar 

  31. Prylutskyy YI, Vereschaka IV, Maznychenko AV, Bulgakova NV, Gonchar OO, Kyzyma OA, et al. C60 fullerene as promising therapeutic agent for correcting and preventing skeletal muscle fatigue. J Nanobiotechnology. 2017;15:8.

    Article  Google Scholar 

  32. Lynchak OV, Prylutskyy YuI, Rybalchenko VK, Kyzyma OA, Soloviov D, Kostjukov VV, et al. Comparative analysis of the antineoplastic activity of C60 fullerene with 5-fluorouracil and pyrrole derivative in vivo. Nanoscale Res Lett. 2017;12:8.

    Article  CAS  Google Scholar 

  33. Scharff P, Carta-Abelmann L, Siegmund C, Matyshevska OP, Prylutska SV, Koval TV, et al. Effect of X-ray and UV irradiation of the C60 fullerene aqueous solution on biological samples. Carbon N Y. 2004;42:1199–201.

    Article  CAS  Google Scholar 

  34. Kuklin AI, Islamov AKh, Gordeliy VI. Two-detector system for small-angle neutron scattering instrument. Neutron News. 2005;16:16–8.

    Article  Google Scholar 

  35. Soloviev AG, Solovieva TM, Stadnik AV, Islamov AH, Kuklin AI. The upgrade of package for preliminary treatment of small-angle scattering spectra. JINR Commun. 2003;10:2003–86.

    Google Scholar 

  36. Shen XH, Tang QY, Huang J, Cai W. Vitamin E regulates adipocytokine expression in a rat model of dietary-induced obesity. Exp Biol Med (Maywood). 2010;235:47–51.

    Article  Google Scholar 

  37. Novelli EL, Diniz YS, Galhardi CM, Ebaid GM, Rodrigues HG, Mani F, et al. Anthropometrical parameters and markers of obesity in rats Laboratory Animals Ltd. Lab Anim. 2007;41:111–19.

    Article  CAS  Google Scholar 

  38. Nedzvetsky V, Andrievsky G, Chachibaia T, Tykhomyrov A. Differences in antioxidant/protective efficacy of hydrated C60 fullerene nanostructures in liver and brain of rats with streptozotocin-induced diabetes. J. Diabetes Metab. 2012;3:2–9.

    Article  Google Scholar 

  39. Sirota TV. A novel approach to study the reaction of adrenaline autooxidation: A possibility for polarographic determination of superoxide dismutase activity and antioxidant properties of various preparations. Biochemistry. 2011;3:253–9.

    Article  Google Scholar 

  40. Korolyuk MA, Ivanova LI, Maiorova IG, Tokarev VE. Method for determining the activity of catalase. Lab. Delo. 1988;1:16–9.

  41. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;2:248–54.

    Article  Google Scholar 

  42. Lyon DY, Adams LK, Falkner JC, Alvarez PJ. Antibacterial activity of fullerene water suspensions: Effects of preparation method and particle size. J. Environ. Sci. Tech. 2006;40:4360–66.

    Article  CAS  Google Scholar 

  43. Zhang B, Bian W, Pal A, He Y. Macrophage apoptosis induced by aqueous C60 aggregates changing the mitochondrial membrane potential. Environ Toxicol Pharmacol. 2015;39:237–46.

    Article  CAS  Google Scholar 

  44. Song M, Liu S, Yin J, Wang H. Interaction of human serum album and C60 aggregates in solution. Int J Mol Sci. 2011;12:4964–74.

    Article  CAS  Google Scholar 

  45. Gelderman MP, Simakova O, Clogston JD, Patri AK, Siddiqui SF, Vostal AC, et al. Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro. Int J Nanomed. 2008;3:59–68.

    CAS  Google Scholar 

  46. Prylutska S, Bilyy R, Overchuk M, Bychko A, Andreichenko K, Stoika R, et al. Water-soluble pristine fullerenes C60 increase the specific conductivity and capacity of lipid model membrane and form the channels in cellular plasma membrane. J. Biomed. Nanotechnol. 2012;8:522–7.

    Article  CAS  Google Scholar 

  47. Prylutska SV, Matyshevska OP, Grynyuk II, Prylutskyy YI, Ritter U, Scharff P. Biological effects of C60 fullerenes in vitro and in a model system. Mol. Cryst. Liq. Cryst. 2007;468:265–74.

    Article  Google Scholar 

  48. Glatter O. A new method for the evaluation of small-angle scattering data. J. Appl. Cryst. 1977;10:415–21.

    Article  Google Scholar 

  49. Svergun DI. Determination of the Regnlarization Parameter in Indirect-Transform Methods Using Perceptual Criteria. J. Appl. Cryst. 1992;25:495–503.

    Article  CAS  Google Scholar 

  50. Prilutski Y, Durov S, Bulavin L, Pogorelov V, Astashkin Y, Yashchuk V, et al. Study of structure of colloidal particles of fullerenes in water solution. Mol.Cryst.Liq.Cryst. 1998;324:65–70.

    Article  CAS  Google Scholar 

  51. Prylutskyy YuI, Durov SS, Bulavin LA, Adamenko II, Moroz KO, Geru II, et al. Structure and thermophysical properties of fullerene C60 aqueous solutions. Int. J. Thermophys. 2001;22:943–56.

    Article  CAS  Google Scholar 

  52. Malafaia AB, Nassif PA, Ribas CA, Ariede BL, Sue KN, Cruz MA. Obesity induction with high fat sucrose in rats. Arq Bras Cir Dig. 2013;26:17–21.

    Article  Google Scholar 

  53. Konukoğlu D, Serin O, Ercan M, Turhan MS. Plasma homocysteine levels in obese and non-obese subjects with or without hypertension; its relationship with oxidative stress and copper. Clin Biochem. 2003;36:405–08.

    Article  Google Scholar 

  54. Prylutska SV, Grynyuk II, Matyshevska OP, Prylutskyy YI, Ritter U, Scharff P. Anti-oxidant properties of C60 fullerenes in vitro. Fullerenes, Nanotubes, Carbon Nanostruct. 2008;16:698–705.

    Article  CAS  Google Scholar 

  55. Grant RW, Dixit VD. Adipose tissue as an immunological organ. Obesity (Silver Spring). 2015;23:512–18.

    Article  CAS  Google Scholar 

  56. Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011;121:2111–7.

    Article  CAS  Google Scholar 

  57. Yang H, Youm YH, Vandanmagsar B, Ravussin A, Gimble JM, Greenway F, et al. Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resistance. J Immunol. 2010;185:1836–45.

    Article  CAS  Google Scholar 

  58. Nozdrenko DM, Zavodovsky DO, Matvienko TYu. C60 fullerene as promising therapeutic agent for the prevention and correction of functioning skeletal muscle at ischemic injury. Nanoscale Res Lett. 2017;12:115.

    Article  CAS  Google Scholar 

  59. Bullard-Dillard R, Creek KE, Scrivens WA, Tour JM. Tissue sites of uptake of 14C-labeled C60. Bioorg Chem. 1996;24:376–85.

    Article  CAS  Google Scholar 

  60. Peiris AN, Struve MF, Mueller RA, Lee MB, Kissebah AH. Glucose metabolism in obesity: influence of body fat distribution. J Clin Endocrinol Metab. 1988;67:760–7.

    Article  CAS  Google Scholar 

  61. Peiris AN, Mueller RA, Smith GA, Struve MF, Kissebah AH. Splanchnic insulin metabolism in obesity. Influence of body fat distribution. J Clin Invest. 1986;78:1648–57.

    Article  CAS  Google Scholar 

  62. Green CJ, Hodson L. The influence of dietary fat on liver fat accumulation. Nutrients. 2014;6:5018–33.

    Article  Google Scholar 

  63. DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes. 1981;30:1000–7.

    Article  CAS  Google Scholar 

  64. Evans DJ, Murray R, Kissebah AH. Relationship between skeletal muscle insulin resistance, insulin-mediated glucose disposal, and insulin binding. Effects of obesity and body fat topography. J Clin Invest. 1984;74:1515–25.

    Article  CAS  Google Scholar 

  65. Nozdrenko D, Prylutskyy Yu, Ritter U, Scharff P. Protective effect of water-soluble pristine C60 fullerene in ischemia-reperfusion injury of skeletal muscle. Int. J. Physiol. Pathophysiol. 2014;5:97–110.

    Article  Google Scholar 

  66. Prylutska S, Grynyuk I, Matyshevska O, Prylutskyy Y, Evstigneev M, Scharff P, et al. C60 fullerene as synergistic agent in tumor-inhibitory doxorubicin treatment. Drugs R D. 2014;14:333–40.

    Article  CAS  Google Scholar 

  67. Afanasieva KS, Prylutska SV, Lozovik AV, Bogutska KI, Sivolob AV, Prylutskyy YuI, et al. С60 fullerene prevents genotoxic effect of doxorubicin on human lymphocytes in vitro. Ukr. Biochem. J. 2015;87:91–8.

    Article  CAS  Google Scholar 

  68. Waki H, Tontonoz P. Endocrine functions of adipose tissue. Annu Rev Pathol. 2007;2:31–56.

    Article  CAS  Google Scholar 

  69. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–7.

    Article  CAS  Google Scholar 

  70. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116:1793–801.

    Article  CAS  Google Scholar 

  71. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Ann. Rev. Immunol. 2011;29:415–45.

    Article  CAS  Google Scholar 

  72. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11:85–97.

    Article  CAS  Google Scholar 

  73. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117:175–84.

    Article  CAS  Google Scholar 

  74. Lacey DC, Achuthan A, Fleetwood AJ, Dinh H, Roiniotis J, Scholz GM, et al. Defining GM-CSF- and macrophage-CSF-dependent macrophage responses by in vitro models. J Immunol. 2012;188:5752–65.

    Article  CAS  Google Scholar 

  75. Winkler G, Dworak O, Salamon F, Salamon D, Speer G, Cseh K. Increased interleukin-12 plasma concentrations in both, insulin-dependent and non-insulin-dependent diabetes mellitus. Diabetologia. 1998;41:488.

    Article  CAS  Google Scholar 

  76. Wegner M, Winiarska H, Bobkiewicz-Kozlowska T, Dworacka M. IL-12 serum levels in patients with type 2 diabetes treated with sulphonylureas. Cytokine. 2008;42:312–6.

    Article  CAS  Google Scholar 

  77. O’Rourke RW, White AE, Metcalf MD, Winters BR, Diggs BS, Zhu X, et al. Systemic inflammation and insulin sensitivity in obese IFN-gamma knockout mice. Metabolism. 2012;61:1152–61.

    Article  Google Scholar 

  78. Pollard KM, Cauvi DM, Toomey CB, Morris KV, Kono DH. Interferon-gamma and systemic autoimmunity. Discov Med. 2013;16:123–31.

    PubMed  PubMed Central  Google Scholar 

  79. Negrin KA, Roth Flach RJ, DiStefano MT, Matevossian A, Friedline RH, Jung D, et al. IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis. PLoS One. 2014;9:e107265.

    Article  Google Scholar 

  80. Dinarello CA. Blocking IL-1 in systemic inflammation. J Exp Med. 2005;201:1355–9.

    Article  CAS  Google Scholar 

  81. Donath MY, Storling J, Berchtold LA, Billestrup N, Mandrup-Poulsen T. Cytokines and ß-cell biology: from concept to clinical translation. Endocr Rev. 2008;29:334–50.

    Article  CAS  Google Scholar 

  82. Dellinger AL, Cunin P, Lee D, Kung AL, Brooks DB, Zhou Z, et al. Inhibition of inflammatory arthritis using fullerene nanomaterials. PLoS One. 2015;10:e0126290.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tetiana Halenova.

Ethics declarations

Conflict of interest

The authors report no potential conflicts of interest relevant to this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Halenova, T., Raksha, N., Vovk, T. et al. Effect of C60 fullerene nanoparticles on the diet-induced obesity in rats. Int J Obes 42, 1987–1998 (2018). https://doi.org/10.1038/s41366-018-0016-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-018-0016-2

This article is cited by

Search

Quick links