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Effects of pepsin and trypsin on the anti-adipogenic action of lactoferrin against pre-adipocytes derived from rat mesenteric fat

  • Tomoji Ono (a1), Satoru Morishita (a1), Chikako Fujisaki (a1), Motoyasu Ohdera (a1), Michiaki Murakoshi (a1) (a2), Norio Iida (a1), Hisanori Kato (a3), Kazuo Miyashita (a4), Masaaki Iigo (a5), Toshihide Yoshida (a2) (a6), Keikichi Sugiyama (a1) (a7) and Hoyoku Nishino (a2) (a7)...

Abstract

Lactoferrin (LF) is a multifunctional glycoprotein in mammalian milk. In a previous report, we showed that enteric-coated bovine LF tablets can decrease visceral fat accumulation, hypothesising that the enteric coating is critical to the functional peptides reaching the visceral fat tissue and exerting their anti-adipogenic activity. The aim of the present study was to assess whether ingested LF can retain its anti-adipogenic activity. We therefore investigated the effects of LF and LF treated with digestive enzymes (the stomach enzyme pepsin and the small intestine enzyme trypsin) on lipid accumulation in pre-adipocytes derived from the mesenteric fat tissue of male Sprague–Dawley rats. Lipid accumulation in pre-adipocytes was significantly reduced by LF in a dose-dependent manner and was associated with reduction in gene expression of CCAAT/enhancer binding protein delta, CCAAT/enhancer binding protein alpha and PPARγ as revealed by DNA microarray analysis. Trypsin-treated LF continued to show anti-adipogenic action, whereas pepsin-treated LF abrogated the activity. When an LF solution (1000 mg bovine LF) was administered by gastric intubation to Sprague–Dawley rats, immunoreactive LF determined by ELISA could be detected in mesenteric fat tissue at a concentration of 14·4 μg/g fat after 15 min. The overall results point to the importance of enteric coating for action of LF as a visceral fat-reducing agent when administered in oral form.

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Copyright

Corresponding author

*Corresponding author: T. Ono, fax +81 465 48 4079, email tomoono@lion.co.jp

References

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1Tomita, M, Bellamy, W, Takase, M, et al. (1991) Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin. J Dairy Sci 74, 41374142.
2Harmsen, MC, Swart, PJ, de Béthune, MP, et al. (1995) Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. J Infect Dis 172, 380388.
3Zimecki, M, Właszczyk, A, Cheneau, P, et al. (1998) Immunoregulatory effects of a nutritional preparation containing bovine lactoferrin taken orally by healthy individuals. Arch Immunol Ther Exp (Warsz) 46, 231240.
4Shoji, H, Oguchi, S, Shinohara, K, et al. (2007) Effects of iron-unsaturated human lactoferrin on hydrogen peroxide-induced oxidative damage in intestinal epithelial cells. Pediatr Res 61, 8992.
5Sekine, K, Ushida, Y, Kuhara, T, et al. (1997) Inhibition of initiation and early stage development of aberrant crypt foci and enhanced natural killer activity in male rats administered bovine lactoferrin concomitantly with azoxymethane. Cancer Lett 121, 211216.
6Yagi, M, Suzuki, N, Takayama, T, et al. (2008) Lactoferrin suppress the adipogenic differentiation of MC3T3-G2/PA6 cells. J Oral Sci 50, 419425.
7Kodama, HA, Amagi, Y, Koyama, H, et al. (1982) A new preadipose cell line derived from newborn mouse calvaria can promote the proliferation of pluripotent hemopoietic stem cells in vitro. J Cell Physiol 112, 8995.
8Moreno-Navarrete, JM, Ortega, FJ, Ricart, W, et al. (2009) Lactoferrin increases (172Thr) AMPK phosphorylation and insulin-induced (p473Ser)AKT while impairing adipocyte differentiation. Int J Obes (Lond) 33, 9911000.
9Tomita, M, Bellamy, W, Takase, M, et al. (1991) Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin. J Dairy Sci 74, 41374142.
10Shimizu, K, Sakai, M, Ando, M, et al. (2006) Newly developed primary culture of rat visceral adipocytes and their in vitro characteristics. Cell Biol Int 30, 381388.
11Mineo, H, Oda, C, Chiji, H, et al. (2007) Thiazolidinediones exhibit different effects on preadipocytes isolated from rat mesenteric fat tissue and cell line 3T3-L1 cells derived from mice. Cell Biol Int 31, 703710.
12Otto, TC & Lane, MD (2005) Adipose development: from stem cell to adipocyte. Crit Rev Biochem Mol Biol 40, 229242.
13Herz, J & Strickland, DK (2001) LRP: a multifunctional scavenger and signaling receptor. J Clin Invest 108, 779784.
14Crawford, SE & Borensztajn, J (1999) Plasma clearance and liver uptake of chylomicron remnants generated by hepatic lipase lipolysis: evidence for a lactoferrin-sensitive and apolipoprotein E-independent pathway. J Lipid Res 40, 797805.
15Hofmann, SM, Zhou, L, Perez-Tilve, D, et al. (2007) Adipocyte LDL receptor-related protein-1 expression modulates postprandial lipid transport and glucose homeostasis in mice. J Clin Invest 117, 32713282.
16Grey, A, Banovic, T, Zhu, Q, et al. (2004) The low-density lipoprotein receptor-related protein 1 is a mitogenic receptor for lactoferrin in osteoblastic cells. Mol Endocrinol 18, 22682278.
17Wakabayashi, H, Takase, M & Tomita, M (2003) Lactoferricin derived from milk protein lactoferrin. Curr Pharm Des 9, 12771287.
18Takayama, Y, Mizumachi, K & Takezawa, T (2002) The bovine lactoferrin region responsible for promoting the collagen gel contractile activity of human fibroblasts. Biochem Biophys Res Commun 299, 813817.
19Fischer, R, Debbabi, H, Blais, A, et al. (2007) Uptake of ingested bovine lactoferrin and its accumulation in adult mouse tissues. Int Immunopharmacol 7, 13871393.
20Talukder, MJ, Takeuchi, T & Harada, E (2003) Characteristics of lactoferrin receptor in bovine intestine: higher binding activity to the epithelium overlying Peyer's patches. J Vet Med A Physiol Pathol Clin Med 50, 123131.
21Takeuchi, T, Kitagawa, H & Harada, E (2004) Evidence of lactoferrin transportation into blood circulation from intestine via lymphatic pathway in adult rats. Exp Physiol 89, 263270.
22Moguilevsky, N, Retegui, LA, Courtoy, PJ, et al. (1984) Uptake of lactoferrin by the liver III. Critical role of the protein moiety. Lab Invest 50, 335340.

Keywords

Effects of pepsin and trypsin on the anti-adipogenic action of lactoferrin against pre-adipocytes derived from rat mesenteric fat

  • Tomoji Ono (a1), Satoru Morishita (a1), Chikako Fujisaki (a1), Motoyasu Ohdera (a1), Michiaki Murakoshi (a1) (a2), Norio Iida (a1), Hisanori Kato (a3), Kazuo Miyashita (a4), Masaaki Iigo (a5), Toshihide Yoshida (a2) (a6), Keikichi Sugiyama (a1) (a7) and Hoyoku Nishino (a2) (a7)...

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