Silk and silkworm pupa peptides suppress adipogenesis in preadipocytes and fat accumulation in rats fed a high-fat diet
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.
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.
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.
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.
KeywordsSilk peptide Silkworm pupa peptide Adipogenesis Obesity Hyperlipidemia Steatosis
- 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
- 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
- 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
- 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.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
- 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.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
- 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
- 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.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
- 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.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.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
- 35.Despres JP (1998) The insulin resistance-dyslipidemic syndrome of visceral obesity: effect on patient’s risk. Obes Res 6:8S–17SGoogle Scholar
- 37.Morrison RF, Farmer SR (2000) Hormonal signaling and transcriptional control of adipocyte differentiation. J Nutr 130:3116S–3121SGoogle Scholar
- 38.Ntambi JM, Kim YC (2000) Adipocyte differentiation and gene expression. J Nutr 130:3122S–3126SGoogle Scholar
- 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