Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Effect of combined mulberry leaf and fruit extract on liver and skin cholesterol transporters in high fat diet-induced obese mice

  • Valacchi, Giuseppe (Department of Life Sciences and Biotechnology, University of Ferrara) ;
  • Belmonte, Giuseppe (Dipartimento di Scienze Mediche, Chirurgiche e Neuroscienze, University of Siena) ;
  • Miracco, Clelia (Dipartimento di Scienze Mediche, Chirurgiche e Neuroscienze, University of Siena) ;
  • Eo, Hyeyoon (Department of Food and Nutrition, Kyung Hee University) ;
  • Lim, Yunsook (Department of Food and Nutrition, Kyung Hee University)
  • Received : 2013.07.31
  • Accepted : 2013.11.14
  • Published : 2014.01.25
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Abstract

Obesity is an epidemic disease characterized by an increased inflammatory state and chronic oxidative stress with high levels of pro-inflammatory cytokines and lipid peroxidation. Moreover, obesity alters cholesterol metabolism with increases in low-density lipoprotein (LDL) cholesterols and triglycerides and decreases in high-density lipoprotein (HDL) cholesterols. It has been shown that mulberry leaf and fruit ameliorated hyperglycemic and hyperlipidemic conditions in obese and diabetic subjects. We hypothesized that supplementation with mulberry leaf combined with mulberry fruit (MLFE) ameliorate cholesterol transfer proteins accompanied by reduction of oxidative stress in the high fat diet induced obesity. Mice were fed control diet (CON) or high fat diet (HF) for 9 weeks. After obesity was induced, the mice were administered either the HF or the HF with combination of equal amount of mulberry leaf and fruit extract (MLFE) at 500mg/kg/day by gavage for 12 weeks. MLFE treatment ameliorated HF induced oxidative stress demonstrated by 4-hydroxynonenal (4-HNE) and modulated the expression of 2 key proteins involved in cholesterol transfer such as scavenger receptor class B type 1 (SR-B1) and ATP-binding cassette transporter A1 (ABCA1) in the HF treated animals. This effect was mainly noted in liver tissue rather than in cutaneous tissue. Collectively, this study demonstrated that MLFE treatment has beneficial effects on the modulation of high fat diet-induced oxidative stress and on the regulation of cholesterol transporters. These results suggest that MLFE might be a beneficial substance for conventional therapies to treat obesity and its complications.

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References

  1. Brundtland GH. From the World Health Organization. Reducing risks to health, promoting healthy life. JAMA 2002;288:1974. https://doi.org/10.1001/jama.288.16.1974
  2. Fernández-Sánchez A, Madrigal-Santillán E, Bautista M, Esquivel- Soto J, Morales-González A, Esquivel-Chirino C, Durante- Montiel I, Sánchez-Rivera G, Valadez-Vega C, Morales-González JA. Inflammation, oxidative stress, and obesity. Int J Mol Sci 2011;12:3117-32. https://doi.org/10.3390/ijms12053117
  3. Kopelman PG. Obesity as a medical problem. Nature 2000;404: 635-43.
  4. Esposito K, Ciotola M, Schisano B, Misso L, Giannetti G, Ceriello A, Giugliano D. Oxidative stress in the metabolic syndrome. J Endocrinol Invest 2006;29:791-5. https://doi.org/10.1007/BF03347372
  5. Pitocco D, Zaccardi F, Di Stasio E, Romitelli F, Santini SA, Zuppi C, Ghirlanda G. Oxidative stress, nitric oxide, and diabetes. Rev Diabet Stud 2010;7:15-25. https://doi.org/10.1900/RDS.2010.7.15
  6. Mukhtar H, Elmets CA. Photocarcinogenesis: mechanisms, models and human health implications. Photochem Photobiol 1996;63: 356-7. https://doi.org/10.1111/j.1751-1097.1996.tb03040.x
  7. Shindo Y, Witt E, Packer L. Antioxidant defense mechanisms in murine epidermis and dermis and their responses to ultraviolet light. J Invest Dermatol 1993;100:260-5. https://doi.org/10.1111/1523-1747.ep12469048
  8. Shindo Y, Witt E, Han D, Epstein W, Packer L. Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. J Invest Dermatol 1994;102:122-4. https://doi.org/10.1111/1523-1747.ep12371744
  9. Mattson MP. Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Exp Gerontol 2009;44:625-33. https://doi.org/10.1016/j.exger.2009.07.003
  10. Vincent HK, Powers SK, Dirks AJ, Scarpace PJ. Mechanism for obesity-induced increase in myocardial lipid peroxidation. Int J Obes Relat Metab Disord 2001;25:378-88. https://doi.org/10.1038/sj.ijo.0801536
  11. Fon Tacer K, Rozman D. Nonalcoholic Fatty liver disease: focus on lipoprotein and lipid deregulation. J Lipids 2011;2011:783976.
  12. Trigatti BL, Krieger M, Rigotti A. Influence of the HDL receptor SR-BI on lipoprotein metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol 2003;23:1732-8. https://doi.org/10.1161/01.ATV.0000091363.28501.84
  13. Spady DK, Kearney DM, Hobbs HH. Polyunsaturated fatty acids up-regulate hepatic scavenger receptor B1 (SR-BI) expression and HDL cholesteryl ester uptake in the hamster. J Lipid Res 1999;40:1384-94.
  14. Hatahet W, Cole L, Kudchodkar BJ, Fungwe TV. Dietary fats differentially modulate the expression of lecithin:cholesterol acyltransferase, apoprotein-A1 and scavenger receptor b1 in rats. J Nutr 2003;133:689-94. https://doi.org/10.1093/jn/133.3.689
  15. Roberts CK, Liang K, Barnard RJ, Kim CH, Vaziri ND. HMGCoA reductase, cholesterol 7alpha-hydroxylase, LDL receptor, SR-B1, and ACAT in diet-induced syndrome X. Kidney Int 2004;66:1503-11. https://doi.org/10.1111/j.1523-1755.2004.00914.x
  16. Grefhorst A, Oosterveer MH, Brufau G, Boesjes M, Kuipers F, Groen AK. Pharmacological LXR activation reduces presence of SR-B1 in liver membranes contributing to LXR-mediated induction of HDL-cholesterol. Atherosclerosis 2012;222:382-9. https://doi.org/10.1016/j.atherosclerosis.2012.02.014
  17. Datar R, Kaesemeyer WH, Chandra S, Fulton DJ, Caldwell RW. Acute activation of eNOS by statins involves scavenger receptor- B1, G protein subunit Gi, phospholipase C and calcium influx. Br J Pharmacol 2010;160:1765-72. https://doi.org/10.1111/j.1476-5381.2010.00817.x
  18. Attia N, Fournier N, Vedie B, Cambillau M, Beaune P, Ziegler O, Grynberg A, Paul JL, Guerci B. Impact of android overweight or obesity and insulin resistance on basal and postprandial SR-BI and ABCA1-mediated serum cholesterol efflux capacities. Atherosclerosis 2010;209:422-9. https://doi.org/10.1016/j.atherosclerosis.2009.09.025
  19. Villarreal-Molina MT, Aguilar-Salinas CA, Rodríguez-Cruz M, Riaño D, Villalobos-Comparan M, Coral-Vazquez R, Menjivar M, Yescas-Gomez P, Königsoerg-Fainstein M, Romero-Hidalgo S, Tusie-Luna MT, Canizales-Quinteros S; Metabolic Study Group. The ATP-binding cassette transporter A1 R230C variant affects HDL cholesterol levels and BMI in the Mexican population: association with obesity and obesity-related comorbidities. Diabetes 2007;56:1881-7. https://doi.org/10.2337/db06-0905
  20. Dong SZ, Zhao SP, Wu ZH, Yang J, Xie XZ, Yu BL, Nie S. Curcumin promotes cholesterol efflux from adipocytes related to PPARgamma-LXRalpha-ABCA1 passway. Mol Cell Biochem 2011;358:281-5. https://doi.org/10.1007/s11010-011-0978-z
  21. Beulens JW, Sierksma A, van Tol A, Fournier N, van Gent T, Paul JL, Hendriks HF. Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1. J Lipid Res 2004;45: 1716-23. https://doi.org/10.1194/jlr.M400109-JLR200
  22. Ehlers SJ, Larson SM, Rasmussen HE, Park YK, Lee JY. High-density lipoprotein metabolism in human apolipoprotein B(100) transgenic/brown adipose tissue deficient mice: a model of obesity-induced hyperinsulinemia. Appl Physiol Nutr Metab 2011;36:313-22. https://doi.org/10.1139/h11-003
  23. Yosipovitch G, DeVore A, Dawn A. Obesity and the skin: skin physiology and skin manifestations of obesity. J Am Acad Dermatol 2007;56:901-16. https://doi.org/10.1016/j.jaad.2006.12.004
  24. Seitz O, Schürmann C, Hermes N, Müller E, Pfeilschifter J, Frank S, Goren I. Wound healing in mice with high-fat diet- or ob gene-induced diabetes-obesity syndromes: a comparative study. Exp Diabetes Res 2010;2010:476969.
  25. Wilson JA, Clark JJ. Obesity: impediment to wound healing. Crit Care Nurs Q 2003;26:119-32. https://doi.org/10.1097/00002727-200304000-00006
  26. Lim HH, Yang SJ, Kim Y, Lee M, Lim Y. Combined treatment of mulberry leaf and fruit extract ameliorates obesity-related inflammation and oxidative stress in high fat diet-induced obese mice. J Med Food 2013;16:673-80. https://doi.org/10.1089/jmf.2012.2582
  27. Lim HH, Lee SO, Kim SY, Yang SJ, Lim Y. Anti-inflammatory and antiobesity effects of mulberry leaf and fruit extract on high fat diet-induced obesity. Exp Biol Med (Maywood) 2013;238: 1160-9. https://doi.org/10.1177/1535370213498982
  28. Barrera G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol 2012;2012:137289.
  29. Bełtowski J, Wojcicka G, Gorny D, Marciniak A. The effect of dietary-induced obesity on lipid peroxidation, antioxidant enzymes and total plasma antioxidant capacity. J Physiol Pharmacol 2000;51:883-96.
  30. Sticozzi C, Belmonte G, Pecorelli A, Arezzini B, Gardi C, Maioli E, Miracco C, Toscano M, Forman HJ, Valacchi G. Cigarette smoke affects keratinocytes SRB1 expression and localization via H2O2 production and HNE protein adducts formation. PLoS One 2012;7:e33592. https://doi.org/10.1371/journal.pone.0033592
  31. Valacchi G, Davis PA, Khan EM, Lanir R, Maioli E, Pecorelli A, Cross CE, Goldkorn T. Cigarette smoke exposure causes changes in Scavenger Receptor B1 level and distribution in lung cells. Int J Biochem Cell Biol 2011;43:1065-70. https://doi.org/10.1016/j.biocel.2009.05.014
  32. Sticozzi C, Belmonte G, Pecorelli A, Cervellati F, Leoncini S, Signorini C, Ciccoli L, De Felice C, Hayek J, Valacchi G. Scavenger receptor B1 post-translational modifications in Rett syndrome. FEBS Lett 2013;587:2199-204. https://doi.org/10.1016/j.febslet.2013.05.042
  33. Fluiter K, Vietsch H, Biessen EA, Kostner GM, van Berkel TJ, Sattler W. Increased selective uptake in vivo and in vitro of oxidized cholesteryl esters from high-density lipoprotein by rat liver parenchymal cells. Biochem J 1996;319:471-6. https://doi.org/10.1042/bj3190471
  34. Mardones P, Strobel P, Miranda S, Leighton F, Quiñones V, Amigo L, Rozowski J, Krieger M, Rigotti A. Alpha-tocopherol metabolism is abnormal in scavenger receptor class B type I (SR-BI)-deficient mice. J Nutr 2002;132:443-9.
  35. Tsuruoka H, Khovidhunkit W, Brown BE, Fluhr JW, Elias PM, Feingold KR. Scavenger receptor class B type I is expressed in cultured keratinocytes and epidermis. Regulation in response to changes in cholesterol homeostasis and barrier requirements. J Biol Chem 2002;277:2916-22. https://doi.org/10.1074/jbc.M106445200
  36. Moran-Ramos S, Avila-Nava A, Tovar AR, Pedraza-Chaverri J, Lopez-Romero P, Torres N. Opuntia ficus indica (nopal) attenuates hepatic steatosis and oxidative stress in obese Zucker (fa/fa) rats. J Nutr 2012;142:1956-63. https://doi.org/10.3945/jn.112.165563
  37. Parola M, Pinzani M, Casini A, Albano E, Poli G, Gentilini A, Gentilini P, Dianzani MU. Stimulation of lipid peroxidation or 4-hydroxynonenal treatment increases procollagen $\alpha$1 (I) gene expression in human liver fat-storing cells. Biochem Biophys Res Commun 1993;194:1044-50. https://doi.org/10.1006/bbrc.1993.1927
  38. Sarada S, Himadri P, Mishra C, Geetali P, Ram MS, Ilavazhagan G. Role of oxidative stress and NFkB in hypoxia-induced pulmonary edema. Exp Biol Med (Maywood) 2008;233:1088-98. https://doi.org/10.3181/0712-RM-337
  39. Kalpana S, Dhananjay S, Anju B, Lilly G, Sai Ram M. Cobalt chloride attenuates hypobaric hypoxia induced vascular leakage in rat brain: molecular mechanisms of action of cobalt chloride. Toxicol Appl Pharmacol 2008;231:354-63. https://doi.org/10.1016/j.taap.2008.05.008
  40. Hang CH, Shi JX, Li JS, Wu W, Yin HX. Concomitant upregulation of nuclear factor-kB activity, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma in a rat model. Neurol India 2005;53:312-7. https://doi.org/10.4103/0028-3886.16930
  41. Oram JF, Vaughan AM. ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins. Curr Opin Lipidol 2000;11:253-60. https://doi.org/10.1097/00041433-200006000-00005
  42. Srivastava N. ATP binding cassette transporter A1--key roles in cellular lipid transport and atherosclerosis. Mol Cell Biochem 2002;237:155-64. https://doi.org/10.1023/A:1016506221047
  43. Valacchi G, Vasu VT, Yokohama W, Corbacho AM, Phung A, Lim Y, Aung HH, Cross CE, Davis PA. Lung vitamin E transport processes are affected by both age and environmental oxidants in mice. Toxicol Appl Pharmacol 2007;222:227-34. https://doi.org/10.1016/j.taap.2007.04.010
  44. Sticozzi C, Pecorelli A, Belmonte G, Valacchi G. Cigarette smoke affects ABCAl expression via liver X receptor nuclear translocation in human keratinocytes. Int J Mol Sci 2010;11: 3375-86. https://doi.org/10.3390/ijms11093375
  45. Kim SY, Lee WC, Kim HB, Kim AJ, Kim SK. Antihyperlipidemic effects of methanol extracts from mulberry leaves in cholesterol-induced hyperlipidemia rats. J Korean Soc Food Sci Nutr 1998;27:1217-22.
  46. Park SH, Jang MJ, Hong JH, Rhee SJ, Choi KH, Park MR. Effects of mulberry leaf extract feeding on lipid status of rats fed high cholesterol diets. J Korean Soc Food Sci Nutr 2007; 36:43-50. https://doi.org/10.3746/jkfn.2007.36.1.043
  47. Yang X, Yang L, Zheng H. Hypolipidemic and antioxidant effects of mulberry (Morus alba L.) fruit in hyperlipidaemia rats. Food Chem Toxicol 2010;48:2374-9. https://doi.org/10.1016/j.fct.2010.05.074
  48. Lee J, Chae K, Ha J, Park BY, Lee HS, Jeong S, Kim MY, Yoon M. Regulation of obesity and lipid disorders by herbal extracts from Morus alba, Melissa officinalis, and Artemisia capillaris in high-fat diet-induced obese mice. J Ethnopharmacol 2008;115: 263-70. https://doi.org/10.1016/j.jep.2007.09.029

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