European Journal of Nutrition

, Volume 51, Issue 8, pp 1011–1019 | Cite as

Silk and silkworm pupa peptides suppress adipogenesis in preadipocytes and fat accumulation in rats fed a high-fat diet

  • Sun Hee Lee
  • Dongsun Park
  • Goeun Yang
  • Dae-Kwon Bae
  • Yun-Hui Yang
  • Tae Kyun Kim
  • Dajeong Kim
  • Jangbeen Kyung
  • Sungho Yeon
  • Kyo Chul Koo
  • Jeong-Yong Lee
  • Seock-Yeon Hwang
  • Seong Soo Joo
  • Yun-Bae Kim
Original Contribution

Abstract

Purpose

The objective was to confirm the anti-obesity activity of a silk peptide (SP) and a silkworm pupa peptide (SPP) in rats fed a high-fat diet (HFD) and to elucidate their action mechanism(s) in a preadipocyte culture system.

Methods

In an in vitro mechanistic study, the differentiation and maturation of 3T3-L1 preadipocytes were stimulated with insulin (5 μg/mL), and effects of SP and SPP on the adipogenesis of mature adipocytes were assessed. In an in vivo anti-obesity study, male C57BL/6 mice were fed an HFD containing SP or SPP (0.3, 1.0, or 3.0%) for 8 weeks, and blood and tissue parameters of obesity were analyzed.

Results

Hormonal stimulation of preadipocytes led to a 50–70% increase in adipogenesis. Polymerase chain reaction and Western blot analyses revealed increases in adipogenesis-specific genes (leptin and Acrp30) and proteins (peroxisome proliferator-activated receptor-γ and Acrp30). The hormone-induced adipogenesis and activated gene expression was substantially inhibited by treatment with SP and SPP (1–50 μg/mL). The HFD markedly increased body weight gain by increasing the weight of epididymal and mesenteric fat. Body and fat weights were significantly reduced by SP and SPP, in which decreases in the area of abdominal adipose tissue and the size of epididymal adipocytes were confirmed by magnetic resonance imaging and microscopic examination, respectively. Long-term HFD caused hepatic lipid accumulation and increased blood triglycerides and cholesterol, in addition to their regulatory factors Acrp30 and leptin. However, SP and SPP recovered the concentrations of Acrp30 and leptin, and attenuated steatosis.

Conclusions

SP and SPP inhibit the differentiation of preadipocytes and adipogenesis by modulating signal transduction pathways and improve HFD-induced obesity by reducing lipid accumulation and the size of adipocytes.

Keywords

Silk peptide Silkworm pupa peptide Adipogenesis Obesity Hyperlipidemia Steatosis 

Supplementary material

394_2011_280_MOESM1_ESM.doc (4 mb)
Supplementary material 1 (DOC 4063 kb)

References

  1. 1.
    Hill JO, Peters JC, Wyatt HR (2007) The Role of public policy in treating the epidemic of global obesity. Clin Pharmacol Ther 81:772–775CrossRefGoogle Scholar
  2. 2.
    Manson JE, Willet WC, Stamfer MJ, Colditz GA, Hunter DJ, Hankinson SE, Hennekens CH, Speizer FE (1995) Body weight and mortality among woman. N Engl J Med 333:677–685CrossRefGoogle Scholar
  3. 3.
    Hill JO, Holly RW, Reed GW, Peters JC (2003) Obesity and the environment: where do we go from here? Science 299:853–855CrossRefGoogle Scholar
  4. 4.
    Hart RW, Keenan KP, Turturro A, Abdo KM, Leakey J, Lyn-Cook L (1995) Calorie restriction and toxicology. Fund Appl Toxicol 25:184–195CrossRefGoogle Scholar
  5. 5.
    Milagro FI, Campion J, Martinez A (2006) Weight gain induce by high-fat feeding involves increased liver oxidation stress. Obes Res 14:1118–1123CrossRefGoogle Scholar
  6. 6.
    Colditz GA, Willett WC, Rotnitzky A, Manson JE (1995) Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 122:481–486Google Scholar
  7. 7.
    Rothwell NJ, Stock MJ (1984) The development of obesity in animals; the role of dietary factors. Clin Endocrinol Metab 13:437–449CrossRefGoogle Scholar
  8. 8.
    Lee JJ, Choi HS, Jeong E, Choi BD, Lee MY (2006) Effect of meal pattern on lipogenesis and lipogenic enzyme activity in rat adipose tissue fed high fat diet. J Korean Soc Food Sci Nutr 35:335–343CrossRefGoogle Scholar
  9. 9.
    Beaumont JL, Carlson LA, Cooper GR, Fejfar Z, Fredrickson DS, Strasser T (1970) Classification of hyperlipidemia and hyperlipoproteinemia. Bull World Health Organ 43:891–915Google Scholar
  10. 10.
    Ahren B, Scheurink AJ (1998) Marked hyperleptinemia after high-fat diet associated with severe glucose intolerance in mice. Eur J Endocrinol 139:461–467CrossRefGoogle Scholar
  11. 11.
    Handa T, Yamaguchi K, Sono Y, Yazawa K (2005) Effects of fenugreek seed extract in obese mice fed a high-fat diet. Biosci Biotechnol Biochem 69:1186–1188CrossRefGoogle Scholar
  12. 12.
    Woods SC, Seeley RJ, Rushing PA, D’Alessio D, Tso P (2003) A controlled high-fat diet induces an obese syndrome in rats. J Nutr 133:1081–1087Google Scholar
  13. 13.
    Vasselli JR, Weindruch R (2005) Intentional weight loss reduces mortality rate in a rodent model of dietary obesity. Obes Res 13:693–702CrossRefGoogle Scholar
  14. 14.
    Murphy TA, Lerch SC (1994) Effects of restricted feeding of growing steers on performance, carcass characteristics, and composition. J Anim Sci 72:2497–2507Google Scholar
  15. 15.
    Cho YM, Park D, Jeon JH, Jang MJ, Kim JJ, Kim JW, Ji HJ, Kim CH, Baek S, Hwang SY, Kim G, Kim YB (2007) Effect of feed restriction in modeling of dietary obesity. Lab Anim Res 23:427–434Google Scholar
  16. 16.
    Surwit RS, Feinglos MN, Rodin J, Sutherland A, Petro AE, Opara EC, Kuhn CM, Rebuffe-Serive M (1995) Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice. Metabolism 44:645–651CrossRefGoogle Scholar
  17. 17.
    Lin S, Thomas TC, Storlien LH, Huang XF (2000) Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice. Int J Obes Relat Metab Disord 24:639–646CrossRefGoogle Scholar
  18. 18.
    Reeves PG (1997) Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr 127(5 Suppl):838S–841SGoogle Scholar
  19. 19.
    Kishino E, Ito T, Fujita K, Kiuchi Y (2006) A mixture of the Salacia reticulata (Kotala himbutu) aqueous extract and cyclodextrin reduces the accumulation of visceral fat mass in mice and rats with high-fat diet-induced obesity. J Nutr 136:433–439Google Scholar
  20. 20.
    Shin M, Park M, Youn M, Lee Y, Nam M, Park I, Jeong Y (2006) Effects of silk protein hydrolysates on blood glucose and serum lipid in db/db diabetic mice. J Korean Soc Food Sci Nutr 35:1343–1348CrossRefGoogle Scholar
  21. 21.
    Lee Y, Park M, Choi J, Kim J, Nam M, Jeong Y (2007) Effects of silk protein hydrolysates on blood glucose level, serum insulin and leptin secretion in OLEFT rats. J Korean Soc Food Sci Nutr 36:703–707CrossRefGoogle Scholar
  22. 22.
    Jung EY, Lee HS, Lee HJ, Kim JM, Lee KW, Suh HJ (2010) Feeding silk protein hydrolysates to C57BL/KsJ-db/db mice improves blood glucose and lipid profiles. Nutr Res 30:783–790CrossRefGoogle Scholar
  23. 23.
    Kim TM, Ryu JM, Seo IK, Lee KM, Yeon S, Kang S, Hwang SY, Kim YB (2008) Effects of red ginseng powder and silk peptide on hypercholesterolemia and atherosclerosis in rabbits. Lab Anim Res 24:67–75Google Scholar
  24. 24.
    Kato N, Sato S, Yamanaka A, Yamada H, Fuwa N, Nomura M (1998) Silk protein, sericin, inhibits lipid peroxidation and tyrosinase activity. Biosci Biotechnol Biochem 62:145–147CrossRefGoogle Scholar
  25. 25.
    Zhaorigetu S, Yanaka N, Sasaki M, Watanabe H, Kato N (2003) Silk protein, sericin, suppresses DMBA-TPA-induced mouse skin tumorigenesis by reducing oxidative stress, inflammatory responses and endogenous tumor promoter TNF-α. Oncol Rep 10:537–543Google Scholar
  26. 26.
    Shin S, Park D, Yeon S, Jeon JH, Kim TK, Joo SS, Lim WT, Lee JY, Kim YB (2009) Stamina-enhancing effects of silk amino acid preparations in mice. Lab Anim Res 25:127–134Google Scholar
  27. 27.
    Shin S, Yeon S, Park D, Oh J, Kang H, Kim S, Joo SS, Lim WT, Lee JY, Choi KC, Kim KY, Kim SU, Kim JC, Kim YB (2010) Silk amino acids improve physical stamina and male reproductive function of mice. Biol Pharm Bull 33:273–278CrossRefGoogle Scholar
  28. 28.
    Choi Y, Lee SM, Kim Y, Jeon G, Sung J, Jeong HS, Lee J (2010) Defatted grape seed extracts suppress adipogenesis in 3T3–L1 preadipocytes. J Korean Soc Food Sci Nutr 39:927–931CrossRefGoogle Scholar
  29. 29.
    Joo SS, Park D, Shin S, Jeon JH, Kim TK, Choi YJ, Lee SH, Kim JS, Park SK, Hwang BY, Lee DI, Kim Y-B (2010) Anti-allergic effects and mechanisms of action of the ethanolic extract of Angelica gigas in dinitrofluorobenzene-induced inflammation models. Environ Toxicol Pharmacol 30:127–133CrossRefGoogle Scholar
  30. 30.
    Hwang JH, Kim DW, Jo EJ, Kim YK, Jo YS, Park JH, Yoo SK, Park MK, Kwak TH, Kho YL, Han J, Choi HS, Lee SH, Kim JM, Lee I, Kyung T, Jang C, Chung J, Kweon GR, Shong M (2009) Pharmacological stimulation of NADH oxidation ameliorates obesity and related phenotypes in mice. Diabetes 58:965–974CrossRefGoogle Scholar
  31. 31.
    Levy JR, Lesko J, Krieg RJ Jr, Robert RA, Stevens W (2000) Leptin responses to glucose infusions in obesity-prone rats. Am J Physiol Endocrinol Metab 279:E1088–E1096Google Scholar
  32. 32.
    Mercer JG, Hoggard N, Morgan PJ (2000) Leptin and obesity; the story so far and it therapeutic implication. CNS Drugs 14:413–424CrossRefGoogle Scholar
  33. 33.
    Visscher TL, Seidell JC (2001) The public health impact of obesity. Annu Rev Public Health 22:355–375CrossRefGoogle Scholar
  34. 34.
    Prineas RJ, Folsom AR, Kaye SA (1993) Central adiposity and increased risk of coronary disease mortality in older women. Ann Epidemiol 3:35–41CrossRefGoogle Scholar
  35. 35.
    Despres JP (1998) The insulin resistance-dyslipidemic syndrome of visceral obesity: effect on patient’s risk. Obes Res 6:8S–17SGoogle Scholar
  36. 36.
    Niklas BJ, Penninx BW, Ryan AS, Berma DM, Lynch NA, Dennis KE (2003) Visceral adipose tissue cutoffs associated with metabolic risk factors for coronary heart disease in women. Diabetes Care 26:1413–1420CrossRefGoogle Scholar
  37. 37.
    Morrison RF, Farmer SR (2000) Hormonal signaling and transcriptional control of adipocyte differentiation. J Nutr 130:3116S–3121SGoogle Scholar
  38. 38.
    Ntambi JM, Kim YC (2000) Adipocyte differentiation and gene expression. J Nutr 130:3122S–3126SGoogle Scholar
  39. 39.
    Kim TK, Park D, Yeon S, Lee SH, Choi YJ, Bae DK, Yang YH, Yang G, Joo SS, Lim WT, Lee JY, Lee J, Jeong HS, Hwang SY, Kim YB (2011) Tyrosine-fortified silk amino acids improve physical function of Parkinson’s disease rats. Food Sci Biotechnol 20:79–84CrossRefGoogle Scholar
  40. 40.
    Park D, Lee SH, Choi YJ, Bae DK, Yang YH, Yang G, Kim TK, Yeon S, Hwang SY, Joo SS, Kim YB (2011) Improving effect of silk peptides on the cognitive function of rats with aging brain facilitated by D-galactose. Biomol Ther 19:224–230CrossRefGoogle Scholar
  41. 41.
    Ryu JM, Kim TM, Seo IK, Yeon S, Lim WT, Lee JY, Hwang SY, O NG, Song J, Lee J, Kim YB (2008) Effect of repeated administration of silk peptide on the immune system of rats. Lab Anim Res 24:361–369Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sun Hee Lee
    • 1
  • Dongsun Park
    • 1
  • Goeun Yang
    • 1
  • Dae-Kwon Bae
    • 1
  • Yun-Hui Yang
    • 1
  • Tae Kyun Kim
    • 1
  • Dajeong Kim
    • 1
  • Jangbeen Kyung
    • 1
  • Sungho Yeon
    • 2
  • Kyo Chul Koo
    • 3
  • Jeong-Yong Lee
    • 3
  • Seock-Yeon Hwang
    • 4
  • Seong Soo Joo
    • 5
  • Yun-Bae Kim
    • 1
  1. 1.College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National UniversityCheongjuKorea
  2. 2.Department of Food Science and TechnologyChungbuk National UniversityCheongjuKorea
  3. 3.Worldway Co., Ltd.JeoneuiKorea
  4. 4.Department of Biomedical Laboratory ScienceDaejeon UniversityDaejeonKorea
  5. 5.Division of Marine Molecular BiotechnologyGangneung-Wonju National UniversityGangneungKorea

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