Journal of Physiology and Biochemistry

, Volume 69, Issue 4, pp 677–686 | Cite as

Curcumin prevents liver fat accumulation and serum fetuin-A increase in rats fed a high-fat diet

  • Yildiz Öner-İyidoğanEmail author
  • Hikmet Koçak
  • Muhammed Seyidhanoğlu
  • Figen Gürdöl
  • Ahmet Gülçubuk
  • Funda Yildirim
  • Aydin Çevik
  • Müjdat Uysal
Original Paper


Fetuin-A is synthesized in the liver and is secreted into the bloodstream. Clinical studies suggest involvement of fetuin-A in metabolic disorders such as visceral obesity, insulin resistance, diabetes, and fatty liver. Curcumin is extracted from the rhizome Curcuma longa and has been shown to possess potent antioxidant, anticarcinogenic, anti-inflammatory, and hypoglycemic properties. In this study, we investigated the effect of curcumin treatment on serum fetuin-A levels as well as hepatic lipids and prooxidant–antioxidant status in rats fed a high-fat diet (HFD). Male Sprague–Dawley rats were divided into six groups. Group 1 was fed control diet (10 % of total calories from fat). Groups 2 and 3 were given curcumin (100 and 400 mg/kg bw/day, respectively ) by gavage for 8 weeks and were fed control diet. Group 4 was fed with HFD (60 % of total calories from fat). Groups 5 and 6 received HFD together with the two doses of curcumin, respectively. Curcumin treatment appeared to be effective in reducing liver triglycerides and serum fetuin-A levels. These findings suggest that the reduction of fetuin-A may contribute to the beneficial effects of curcumin in the pathogenesis of obesity.


Obesity Curcumin Fetuin-A Fatty liver High-fat diet 



This work was supported by the Research Fund of Istanbul University. Project number 8244.


  1. 1.
    Ammon HP, Wahl MA (1991) Pharmacology of Curcuma longa. Planta Med 57:1–7PubMedCrossRefGoogle Scholar
  2. 2.
    Auberger P, Falquerho L, Contreres JO, Pages G, Le Cam G, Rossi B, Le Cam A (1989) Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity. Cell 58:631–640PubMedCrossRefGoogle Scholar
  3. 3.
    Beutler E, Duron O, Kelly BM (1979) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888Google Scholar
  4. 4.
    Bonnefont-Rousselot D, Ratziu V, Giral P, Charlotte F, Beucler I, Poynard T (2006) Blood oxidative stress markers are unreliable markers of hepatic steatosis. Aliment Pharmacol Ther 23:91–98PubMedCrossRefGoogle Scholar
  5. 5.
    Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40:1387–1395PubMedCrossRefGoogle Scholar
  6. 6.
    Buege JA, Aust JD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310PubMedCrossRefGoogle Scholar
  7. 7.
    Catala-Niell A, Estrany ME, Proenza AM, Gianotti M, Llado I (2008) Skeletal muscle and liver oxidative metabolism in response to a voluntary isocaloric intake of a high fat diet in male and female rats. Cell Physiol Biochem 22:327–336PubMedCrossRefGoogle Scholar
  8. 8.
    Chalasani N, Deeg MA, Crabb DW (2004) Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 99:1497–1502PubMedCrossRefGoogle Scholar
  9. 9.
    Chang S, Graham B, Yakubu F, Lin D, Peters JC, Hill JO (1990) Metabolic differences between obesity-prone and obesity-resistant rats. Am J Physiol 259:R1103–R1110PubMedGoogle Scholar
  10. 10.
    Dasgupta S, Bhattacharya S, Biswas A, Majumdar SS, Mukhopadhyay S, Ray S, Bhattacharya S (2010) NF-kappaB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance. Biochem J 429:451–462PubMedCrossRefGoogle Scholar
  11. 11.
    Ejaz A, Wu D, Kwan P, Meydani M (2009) Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr 139:919–925PubMedCrossRefGoogle Scholar
  12. 12.
    Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, Vanni E, Bertelli C, Fatta E, Bignamini D, Marchesini G, Fargion S (2008) Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology 48:792–798PubMedCrossRefGoogle Scholar
  13. 13.
    Ghibaudi L, Cook J, Farley C, van Heek M, Hwa JJ (2002) Fat intake affects adiposity, comorbidity factors, and energy metabolism of Sprague–Dawley rats. Obes Res 10:956–963PubMedCrossRefGoogle Scholar
  14. 14.
    Habig WH, Jacoby WB (1981) Assays for differentiation of glutathione S-transferases. Methods Enzymol 77:398–405PubMedCrossRefGoogle Scholar
  15. 15.
    Haukeland JW, Dahl TB, Yndestad A, Gladhaug IP, Løberg EM, Haaland T, Konopski Z, Wium C, Aasheim ET, Johansen OE, Aukrust P, Halvorsen B, Birkeland KI (2012) Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies. Eur J Endocrinol 166:503–510PubMedCrossRefGoogle Scholar
  16. 16.
    He HJ, Wang GY, Gao Y, Ling WH, Yu ZW, Jin TR (2012) Curcumin attenuates Nrf2 signaling defect, oxidative stress in muscle and glucose intolerance in high fat diet-fed mice. World J Diabetes 15:94–104CrossRefGoogle Scholar
  17. 17.
    Ix JH, Sharma K (2010) Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. J Am Soc Nephrol 21:406–412PubMedCrossRefGoogle Scholar
  18. 18.
    Jacob A, Wu R, Zhou M, Wang P (2007) Mechanism of the anti-inflammatory effect of curcumin: PPAR-gamma activation. PPAR Res 2007:89369Google Scholar
  19. 19.
    Jang EM, Choi MS, Jung UJ, Kim MJ, Kim HJ, Jeon SM, Shin SK, Seong CN, Lee MK (2008) Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat-fed hamsters. Metabolism 57:1576–1583PubMedCrossRefGoogle Scholar
  20. 20.
    Kempaiah RK, Srinivasan K (2004) Antioxidant status of red blood cells and liver in hypercholesterolemic rats fed hypolipidemic spices. Int J Vitam Nutr Res 74:199–208PubMedCrossRefGoogle Scholar
  21. 21.
    Levin BE, Dunn-Meynell AA (2006) Differential effects of exercise on body weight gain and adiposity in obesity-prone and -resistant rats. Int J Obes 30:722–777CrossRefGoogle Scholar
  22. 22.
    Lewis JR, Mohanty SR (2010) Nonalcoholic fatty liver disease: a review and update. Dig Dis Sci 55:560–578PubMedCrossRefGoogle Scholar
  23. 23.
    Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21:8370–8377PubMedGoogle Scholar
  24. 24.
    Lin X, Braymer HD, Bray GA, York DA (1998) Differential expression of insulin receptor tyrosine kinase inhibitor (fetuin) gene in a model of diet-induced obesity. Life Sci 63:145–153PubMedCrossRefGoogle Scholar
  25. 25.
    Manjunatha H, Srinivasan K (2007) Hypolipidemic and antioxidant effects of curcumin and capsaicin in high-fat–fed rats. Can J Physiol Pharmacol 85:588–596PubMedCrossRefGoogle Scholar
  26. 26.
    Manjunatha H, Srinivasan K (2007) Hypolipidemic and antioxidant effects of dietary curcumin and capsaicin in induced hypercholesterolemic rats. Lipids 42:1133–1142PubMedCrossRefGoogle Scholar
  27. 27.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 7:412–419CrossRefGoogle Scholar
  28. 28.
    Menon VP, Sudheer AR (2007) Antioxidant and anti-inflammatory properties of curcumin. Adv Exp Med Biol 595:105–125PubMedCrossRefGoogle Scholar
  29. 29.
    Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, Sterling RK, Shiffman ML, Stravitz RT, Sanyal AJ (2003) Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 37:1286–1292PubMedCrossRefGoogle Scholar
  30. 30.
    Mori K, Emoto M, Araki T, Yokoyama H, Lee E, Teramura M, Koyama H, Shoji T, Inaba M, Nishizawa Y (2008) Effects of pioglitazone on serum fetuin-A levels in patients with type 2 diabetes mellitus. Metabolism 57:1248–1252PubMedCrossRefGoogle Scholar
  31. 31.
    Mori K, Emoto M, Yokoyama H, Araki T, Teramura M, Koyama H, Shoji T, Inaba M, Nishizawa Y (2006) Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care 29:468PubMedCrossRefGoogle Scholar
  32. 32.
    Mylorie AA, Collins H, Umbles C, Kyle J (1986) Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 82:512–520CrossRefGoogle Scholar
  33. 33.
    Nishiyama T, Mae T, Kishida H, Tsukagawa M, Mimaki Y, Kuroda M, Sashida Y, Takahashi K, Kawada T, Nakagawa K, Kitahara M (2005) Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an increase in blood glucose level in type 2 diabetic KK-Ay mice. J Agric Food Chem 53:959–963PubMedCrossRefGoogle Scholar
  34. 34.
    Obika M, Noguchi H (2012) Diagnosis and evaluation of nonalcoholic fatty liver disease. Exp Diabetes Res 2012:145754Google Scholar
  35. 35.
    Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358PubMedCrossRefGoogle Scholar
  36. 36.
    Oliveira CP, da Costa Gayotto LC, Tatai C, Della Bina BI, Janiszewski M, Lima ES, Abdalla DS, Lopasso FP, Laurindo FR, Laudanna AA (2002) Oxidative stress in the pathogenesis of nonalcoholic fatty liver disease, in rats fed with a choline-deficient diet. Journal of Cellular and Molecular Medicine 6:399–406PubMedCrossRefGoogle Scholar
  37. 37.
    Omaye ST, Turnbull JD, Sauberlich HE (1979) Selected methods for the determination of ascorbic acid in animal cells, tissues and fluids. Methods Enzymol 62:3–8PubMedCrossRefGoogle Scholar
  38. 38.
    Reinehr T, Kiess W, de Sousa G, Stoffel-Wagner B, Wunsch R (2006) Intima media thickness in childhood obesity: Relations to inflammatory marker, glucose metabolism, and blood pressure. Metabolism 55:113–118PubMedCrossRefGoogle Scholar
  39. 39.
    Roskams T, Yang SQ, Koteish A, Durnez A, DeVos R, Huang X, Achten R, Verslype C, Diehl AM (2003) Oxidative stress and oval cell accumulation in mice and humans with alcoholic and nonalcoholic fatty liver disease. Am J Pathol 163:1301–1311PubMedCrossRefGoogle Scholar
  40. 40.
    Scapagnini G, Vasto S, Abraham NG, Caruso C, Zella D, Fabio G (2011) Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders. Mol Neurobiol 44:192–201PubMedCrossRefGoogle Scholar
  41. 41.
    Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W (2003) The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 112:357–366PubMedGoogle Scholar
  42. 42.
    Seo KI, Choi MS, Jung UJ, Kim HJ, Yeo J, Jeon SM, Lee MK (2008) Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol Nutr Food Res 52:995–1004PubMedCrossRefGoogle Scholar
  43. 43.
    Shao W, Yu Z, Chiang Y, Yang Y, Chai T, Foltz W, Lu H, Fantus IG, Jin T (2012) Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS One 7:e28784PubMedCrossRefGoogle Scholar
  44. 44.
    Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85PubMedCrossRefGoogle Scholar
  45. 45.
    Smith S (1994) The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. FASEB J 8:1248–1259PubMedGoogle Scholar
  46. 46.
    Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Kröber SM, Machicao F, Fritsche A, Häring HU (2006) Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care 29:853–857PubMedCrossRefGoogle Scholar
  47. 47.
    Tang Y, Chen A (2010) Curcumin protects hepatic stellate cells against leptin-induced activation in vitro by accumulating intracellular lipids. Endocrinology 151:4168–4177PubMedCrossRefGoogle Scholar
  48. 48.
    Torres DM, Harrison SA (2008) Diagnosis and therapy of nonalcoholic steatohepatitis. Gastroenterology 134:1682–1698PubMedCrossRefGoogle Scholar
  49. 49.
    Viollet B, Guigas B, Leclerc J, Hébrard S, Lantier L, Mounier R, Andreelli F, Foretz M (2009) AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives. Acta Physiol 196:81–98CrossRefGoogle Scholar
  50. 50.
    Wei QY, Chen WF, Zhou B, Yang L, Liu ZL (2006) Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues. Biochim Biophys Acta 1760:70–77PubMedCrossRefGoogle Scholar
  51. 51.
    Wieckowska A, Feldstein AE (2008) Diagnosis of nonalcoholic fatty liver disease: invasive versus noninvasive. Seminars in Liver Disease 28:386–395PubMedCrossRefGoogle Scholar
  52. 52.
    Wieckowska A, McCullough AJ, Feldstein AE (2007) Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology 46:582–589PubMedCrossRefGoogle Scholar
  53. 53.
    Yang C, Zhang X, Fan H, Liu Y (2009) Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Res 28:133–141CrossRefGoogle Scholar
  54. 54.
    Yao J, Zhi M, Chen M (2011) Effect of silybin on high-fat-induced fatty liver in rats. Braz J Med Biol Res 44:652–659PubMedGoogle Scholar

Copyright information

© University of Navarra 2013

Authors and Affiliations

  • Yildiz Öner-İyidoğan
    • 1
    Email author
  • Hikmet Koçak
    • 2
  • Muhammed Seyidhanoğlu
    • 1
  • Figen Gürdöl
    • 1
  • Ahmet Gülçubuk
    • 3
  • Funda Yildirim
    • 3
  • Aydin Çevik
    • 4
  • Müjdat Uysal
    • 1
  1. 1.Department of Biochemistry, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey
  2. 2.Department of Biochemistry, Faculty of MedicineIstanbul Bilim UniversityIstanbulTurkey
  3. 3.Department of Pathology, Faculty of Veterinary MedicineIstanbul UniversityIstanbulTurkey
  4. 4.Department of Laboratory Animal Biology and Applied Biomedical Techniques, Institute for Experimental Research and Applied Medical ResearchIstanbul UniversityIstanbulTurkey

Personalised recommendations