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

• Published in: British journal of nutrition 2011-01, Vol.105 (2), p.200-211
• Main Authors: Ono, Tomoji, Morishita, Satoru, Fujisaki, Chikako, Ohdera, Motoyasu, Murakoshi, Michiaki, Iida, Norio, Kato, Hisanori, Miyashita, Kazuo, Iigo, Masaaki, Yoshida, Toshihide, Sugiyama, Keikichi, Nishino, Hoyoku
• Format: Article
• Language: English
• Subjects: Accumulation; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Adipogenesis - drug effects; Adult Stem Cells - cytology; Adult Stem Cells - drug effects; Adult Stem Cells - metabolism; Animals; binding proteins; Biological and medical sciences; Cattle; coatings; enzyme-linked immunosorbent assay; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; gene expression; Glycoproteins; Humans; In Vitro Techniques; Intra-Abdominal Fat - cytology; lactoferrin; Lactoferrin - administration & dosage; Lactoferrin - pharmacokinetics; Lactoferrin - pharmacology; Lipid Metabolism - drug effects; Male; Metabolism and Metabolic Studies; microarray technology; Milk; Obesity, Abdominal - drug therapy; pepsin; Pepsin A - pharmacology; Peptides; Rats; Rats, Sprague-Dawley; Rodents; Small intestine; stomach; Tablets, Enteric-Coated; Tissue Distribution; trypsin; Trypsin - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; visceral fat
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114510003259

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.