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BITC and S-Carvone Restrain High-Fat Diet-Induced Obesity and Ameliorate Hepatic Steatosis and Insulin Resistance

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Abstract

Purpose

To investigate the preventative activity of benzyl isothiocyante and S-carvone against high-fat diet-induced obesity and metabolic complications.

Methods

Ten-week-old C57BL/6 male mice were fed a high-fat diet and injected intraperitoneally twice per week with benzyl isothiocyante, S-carvone, or vehicle for 8 weeks. The body weight, food intake, and body composition were monitored, and glucose tolerance and insulin tolerance tests were performed at the end of the experiment. Serum and tissue samples were studied using serum biochemistry, histological, and gene expression analysis to define the effects of benzyl isothiocyante and S-carvone treatments on lipid and glucose metabolism and inflammatory responses.

Results

Benzyl isothiocyante and S-carvone blocked high-fat diet-induced weight gain, fat accumulation in the liver, and insulin resistance. The beneficial effects were found to be associated with an improvement of expression of macrophage marker genes in white adipose tissue, including F4/80, Cd11b, Cd11c, Cd206, and Tnf-α, and reduced expression of genes (Pparγ2, Scd1, Cd36) responsible for lipid synthesis and transport in the liver.

Conclusion

Benzyl isothiocyante and S-carvone block high-fat diet-induced obesity and metabolism disorders and can be considered for management of the obesity epidemic that affects approximately 36% of adults and 17% of children in the USA.

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Abbreviations

ACC:

Acetyl-CoA carboxylase

AUC:

Area under the curve

BAT:

Brown adipose tissue

BITC:

Benzyl isothiocyanate

DMSO:

Dimethyl sulfoxide

eWAT:

Epididymal white adipose tissues

FAS:

Fatty acid synthase

FFA:

Free fatty acid

GTT:

Glucose tolerance test

HFD:

High-fat diet

HOMA-IR:

Homeostatic model assessment of insulin resistance

ITT:

Insulin tolerance test

iWAT:

Inguinal white adipose tissues

PPARγ:

Peroxisome proliferator-activated receptor-γ

pWAT:

Perirenal white adipose tissues

SCD:

Stearoyl-CoA desaturase

SREBP:

Sterol regulatory element-binding protein

TG:

Triglyceride

TNF-α:

Tumor necrosis factor α

References

  1. Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity among adults and youth: United States. NCHS Data Brief. 2011-2014;2015:1–8.

    Google Scholar 

  2. Pi-Sunyer X. The medical risks of obesity. Postgrad Med. 2009;121:21–33.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Hammond RA, Levine R. The economic impact of obesity in the United States. Diabetes Metab Syndr Obes. 2010;3:285–95.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Monteiro R, Azevedo I. Chronic inflammation in obesity and the metabolic syndrome. Mediat Inflamm. 2010;2010

  5. Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Front Endocrinol (Lausanne). 2016;7:30.

    Google Scholar 

  6. 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  PubMed  PubMed Central  Google Scholar 

  7. Le Lay S, Simard G, Martinez MC, Andriantsitohaina R. Oxidative stress and metabolic pathologies: from an adipocentric point of view. Oxidative Med Cell Longev. 2014;2014:908539.

    Google Scholar 

  8. Cui R, Gao M, Qu S, Liu D. Overexpression of superoxide dismutase 3 gene blocks high-fat diet-induced obesity, fatty liver and insulin resistance. Gene Ther. 2014;21:840–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ma Y, Gao M, Liu D. Chlorogenic acid improves high fat diet-induced hepatic steatosis and insulin resistance in mice. Pharm Res. 2015;32:1200–9.

    Article  CAS  PubMed  Google Scholar 

  10. Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res. 2007;55:224–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Miyoshi N, Takabayashi S, Osawa T, Nakamura Y. Benzyl isothiocyanate inhibits excessive superoxide generation in inflammatory leukocytes: implication for prevention against inflammation-related carcinogenesis. Carcinogenesis. 2004;25:567–75.

    Article  CAS  PubMed  Google Scholar 

  12. Hecht SS. Inhibition of carcinogenesis by isothiocyanates. Drug Metab Rev. 2000;32:395–411.

    Article  CAS  PubMed  Google Scholar 

  13. Lee YM, Seon MR, Cho HJ, Kim JS, Park JH. Benzyl isothiocyanate exhibits anti-inflammatory effects in murine macrophages and in mouse skin. J Mol Med (Berl). 2009;87:1251–61.

    Article  CAS  Google Scholar 

  14. Wu X, Zhou QH, Xu K. Are isothiocyanates potential anti-cancer drugs? Acta Pharmacol Sin. 2009;30:501–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. de Carvalho CC, da Fonseca MMR. Carvone: why and how should one bother to produce this terpene. Food Chem. 2006;95:413–22.

    Article  Google Scholar 

  16. Elmastaş M, Dermirtas I, Isildak O, Aboul-Enein HY. Antioxidant activity of S-Carvone isolated from spearmint (Mentha spicata L. fam Lamiaceae). J Liq Chromatogr Relat Technol. 2006;29:1465–75.

    Article  Google Scholar 

  17. Rajeshwari T, Raja B. Antioxidant and free radical scavenging effect of D-carvone in hypertensive rats. In vivo and in vitro study. Int Lett Nat Sci. 2015;35:6–12.

  18. Sabir S, Singh D, Rocha J. In vitro antioxidant activity of S-Carvone isolated from zanthoxylum alatum. Pharm Chem J. 2015;49:187–91.

    Article  CAS  Google Scholar 

  19. Vinothkumar R, Sudha M, Viswanathan P, Kabalimoorthy J, Balasubramanian T, Nalini N. Modulating effect of d-carvone on 1,2-dimethylhydrazine-induced pre-neoplastic lesions, oxidative stress and biotransforming enzymes, in an experimental model of rat colon carcinogenesis. Cell Prolif. 2013;46:705–20.

    Article  CAS  PubMed  Google Scholar 

  20. Raphael T, Kuttan G. Immunomodulatory activity of naturally occurring monoterpenes carvone, limonene, and perillic acid. Immunopharm Immunot. 2003;25:285–94.

    Article  CAS  Google Scholar 

  21. de Cassia da Silveira e Sa R, Andrade LN, de Sousa DP. A review on anti-inflammatory activity of monoterpenes. Molecules. 2013; 18: 1227–54.

  22. Zheng G-q, Kenney PM, Lam LK. Effects of carvone compounds on glutathione S-transferase activity in a/J mice. J Agr Food Chem. 1992;40:751–5.

    Article  CAS  Google Scholar 

  23. Noeman SA, Hamooda HE, Baalash AA. Biochemical study of oxidative stress markers in the liver, kidney and heart of high fat diet induced obesity in rats. Diabetol Metab Syndr. 2011;3:17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  CAS  PubMed  Google Scholar 

  25. Festi D, Colecchia A, Sacco T, Bondi M, Roda E, Marchesini G. Hepatic steatosis in obese patients: clinical aspects and prognostic significance. Obes Rev. 2004;5:27–42.

    Article  CAS  PubMed  Google Scholar 

  26. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444:840–6.

    Article  CAS  PubMed  Google Scholar 

  27. Bu L, Gao M, Qu S, Liu D. Intraperitoneal injection of clodronate liposomes eliminates visceral adipose macrophages and blocks high-fat diet-induced weight gain and development of insulin resistance. AAPS J. 2013;15:1001–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Darkhal P, Gao M, Ma Y, Liu D. Blocking high-fat diet-induced obesity, insulin resistance and fatty liver by overexpression of Il-13 gene in mice. Int J Obes (Lond). 2015;39:1292–9.

    Article  CAS  Google Scholar 

  29. Yan L, Song K, Gao M, Qu S, Liu D. Modulation of cell-mediated immunity to suppress high fat diet-induced obesity and insulin resistance. Pharm Res. 2016;33:395–403.

    Article  CAS  PubMed  Google Scholar 

  30. Alsanea S, Gao M, Liu D. Phloretin prevents high-fat diet-induced obesity and improves metabolic homeostasis. AAPS J. 2017;19:797–805.

  31. Waterman C, Rojas-Silva P, Tumer TB, Kuhn P, Richard AJ, Wicks S, et al. Isothiocyanate-rich Moringa oleifera extract reduces weight gain, insulin resistance, and hepatic gluconeogenesis in mice. Mol Nutr Food Res. 2015;59:1013–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Inoue M, Ohtake T, Motomura W, Takahashi N, Hosoki Y, Miyoshi S, et al. Increased expression of PPARgamma in high fat diet-induced liver steatosis in mice. Biochem Biophys Res Commun. 2005;336:215–22.

    Article  CAS  PubMed  Google Scholar 

  33. Kotronen A, Seppanen-Laakso T, Westerbacka J, Kiviluoto T, Arola J, Ruskeepaa AL, et al. Hepatic stearoyl-CoA desaturase (SCD)-1 activity and diacylglycerol but not ceramide concentrations are increased in the nonalcoholic human fatty liver. Diabetes. 2009;58:203–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Samuel VT, Petersen KF, Shulman GI. Lipid-induced insulin resistance: unravelling the mechanism. Lancet. 2010;375:2267–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chen L, Chen R, Wang H, Liang F. Mechanisms linking inflammation to insulin resistance. Int J Endocrinol. 2015;2015:508409.

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, 30602, USA

    Sary Alsanea & Dexi Liu

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  1. Sary Alsanea
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  2. Dexi Liu
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Correspondence to Dexi Liu.

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Alsanea, S., Liu, D. BITC and S-Carvone Restrain High-Fat Diet-Induced Obesity and Ameliorate Hepatic Steatosis and Insulin Resistance. Pharm Res 34, 2241–2249 (2017). https://doi.org/10.1007/s11095-017-2230-3

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  • DOI: https://doi.org/10.1007/s11095-017-2230-3

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