Effects of pepsin and trypsin on the anti-adipogenic action of lactoferrin against pre-adipocytes derived from rat mesenteric fat.
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.
Ono
Tomoji
T
Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa 256-0811, Japan. tomoono@lion.co.jp
Morishita
Satoru
S
Fujisaki
Chikako
C
Ohdera
Motoyasu
M
Murakoshi
Michiaki
M
Iida
Norio
N
Kato
Hisanori
H
Miyashita
Kazuo
K
Iigo
Masaaki
M
Yoshida
Toshihide
T
Sugiyama
Keikichi
K
Nishino
Hoyoku
H
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects*; D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002417:Cattle; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D050152:Intra-Abdominal Fat / Q000166:cytology; D007781:Lactoferrin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D056128:Obesity, Abdominal / Q000188:drug therapy; D010434:Pepsin A / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013608:Tablets, Enteric-Coated; D014018:Tissue Distribution; D014357:Trypsin / Q000494:pharmacology*
D013608:Tablets, Enteric-Coated; D007781:Lactoferrin; D014357:Trypsin; D010434:Pepsin A