Anti-obesity activity of hen egg anti-lipase immunoglobulin yolk, a novel pancreatic lipase inhibitor

Nutrition & Metabolism

Satoshi Nagaoka²  Masaya Shimada²  Tsuyoshi Goto²  Sa Van Nguyen¹  Yoshikatsu Kodama¹  Kouji Umeda¹  Rahman Shofiqur¹  Taishi Ando²  Mai Hirose² 

[1] Immunology Research Institute in Gifu, EW Nutrition Japan, Gifu, Japan;Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan

关键词: Mice;    Lipid;    Pancreatic lipase;    IgY;    Obesity;   

Others  :  803038
DOI  :  10.1186/1743-7075-10-70

 received in 2013-09-11, accepted in 2013-12-02,  发布年份 2013

【 摘 要 】

Background

There is completely no report about both hen egg anti-lipase immunoglobulin yolk (IgY) and its anti-obesity action. Thus, we tried to isolate and characterize a novel anti-lipase immunoglobulin from hen egg yolk. Moreover, we investigated whether hen egg yolk anti-lipase IgY inhibits pancreatic lipase activity in vitro, and examined its ability to prevent obesity in a murine high fat diet-induced obesity model.

Methods

We determined the inhibitory action of Anti-lipase IgY on lipase activity in vitro. We also focused our evaluation on the anti-obesity properties of Anti-lipase IgY in a murine high fat diet-induced obesity model.

Results

Anti-lipase IgY blocked porcine lipase activity with an IC₅₀ of 0.49 μM. Supplementing the high fat diet with only 0.2% (w/w) of Anti-lipase IgY for 35 days significantly decreased the weights of intraperitoneal adipose tissues, epididymal, mesenteric, retroperitoneal and perirenal adipose tissues, and the amounts of hepatic total lipid, triglyceride, and cholesterol. This was accompanied by a significant increase in the fecal excretion of triglyceride in the absence of diarrhea. Furthermore, Anti-lipase IgY treatment restored body weight gain to levels similar to mice fed with Control IgY.

Conclusions

This study provides the first report of the development of anti-lipase IgY and the direct evidence that inhibition of pancreatic lipase using Anti-lipase IgY is an effective anti-obesity treatment due to the associated increase in fecal excretion of triglyceride.

【 授权许可】

   
2013 Hirose et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Birari RB, Bhutani KK: Pancreatic lipase inhibitors from natural sources: unexplored potential. Drug Discov Today 2007, 12:879-889.
• [2]Ballinger A, Peikin SR: Orlistat: its current status as an anti-obesity drug. Eur J Pharmacol 2002, 440:109-117.
• [3]Grove KA, Sae-tan S, Kennett MJ, Lambert JD: (−)-Epigallocatechin-3-gallate inhibits pancreatic lipase and reduces body weight gain in high fat-fed obese mice. Obesity 2012, 20:2311-2313.
• [4]Uchiyama S, Taniguchi Y, Saka A, Yoshida A, Yajima H: Prevention of diet-induced obesity by dietary black tea polyphenols extract in vitro and in vivo. Nutrition 2011, 27:287-292.
• [5]Shin JH, Yang M, Nam SW, Kim JT, Myung NH, Bang WG, Roe IH: Use of egg yolk-derived immunoglobulin as an alternative to antibiotic treatment for control of Helicobacter pylori Infection. Clin Diagn Lab Immunol 2002, 9:1061-1066.
• [6]Lee KA, Chang SK, Lee YJ, Lee JH, Koo NS: Acid stability of anti-Helicobacter pyroli IgY in aqueous polyol solution. J Biochem Mol Biol 2002, 35:488-493.
• [7]Hatta H, Tsuda K, Akachi S, Kim M, Yamamoto T, Ebina T: Oral passive immunization effect of anti-human rotavirus IgY and its behavior against proteolytic enzymes. Biosci Biotechnol Biochem 1993, 57:1077-1081.
• [8]Rahman S, Nguyen SV, Icatlo FC Jr, Umeda K, Kodama Y: Oral passive IgY-based immunotherapeutics: a novel solution for prevention and treatment of alimentary tract diseases. Hum Vaccin Immunother 2013, 14:1039-1048.
• [9]Hirai K, Arimitsu H, Umeda K, Yokota K, Shen L, Ayada K, Kodama Y, Tsuji T, Hirai Y, Oguma K: Passive oral immunization by egg yolk immunoglobulin (IgY) to Vibrio cholerae effectively prevents cholera. Acta Med Okayama 2010, 64:163-170.
• [10]Ibrahim ESM, Rahman AK, Isoda R, Umeda K, Nguyen SV, Kodama Y: In vitro and in vivo effectiveness of egg yolk antibody against Candida albicans (anti-CA IgY). Vaccine 2008, 26:2073-2080.
• [11]Neri P, Tokoro S, Kobayashi R, Sugiyama T, Umeda K, Shimizu T, Tsuji T, Kodama Y, Oguma K, Mori H: Specific egg yolk immunoglobulin as a new preventive approach for Shiga-toxin-mediated diseases. PLoS ONE 2011, 6:e26526.
• [12]Rahman S, Higo MK, Htunc KW, Taniguchi K, Icatlo FC, Tsuji T, Kodama Y, Nguyen SV, Umeda K, Oo HN, Myint YY, Htut T, Myint SS, Thura K, Thu HM, Fatmawati NND, Oguma K: Randomized placebo-controlled clinical trial of immunoglobulin Y as adjunct to standard supportive therapy for rotavirus-associated diarrhea among pediatric patients. Vaccine 2012, 30:4661-4669.
• [13]Garner CW, Smith LC: Porcine pancreatic lipase. A glycoprotein. J Biol Chem 1972, 247:561-565.
• [14]Yokoyama H, Hashi T, Umeda K, Icatlo FC Jr, Kuroki M, Ikemori Y, Kodama Y: Effect of oral egg antibody in experimental F18+ Escherichia coli infection in weaned pigs. J Vet Med Sci 1997, 59:917-921.
• [15]Kuroki M, Ikemori Y, Yokoyama H, Peralta RC, Icatlo FC, Kodama Y: Passive protection against bovine rotavirus-induced diarrhea in murine model by specific immunoglobulins from chicken egg yolk. Vet Microbiol 1993, 37:135-146.
• [16]Icatlo FC, Kuroki M, Kobayashi C, Yokoyama H, Ikemori Y, Hashi T, Kodama Y: Affinity purification of Helicobacter pylori urease. Relevance to gastric mucin adherence by urease protein. J Biol Chem 1998, 273:18130-18138.
• [17]Tsujita T, Takaichi H, Takaku T, Aoyama S, Hiraki J: Antiobesity action of epsilon-polylysine, a potent inhibitor of pancreatic lipase. J Lipid Res 2006, 47:1852-1858.
• [18]Folch J, Lees M, Sloane Stanley GH: A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957, 226:497-509.
• [19]Nagaoka S, Miwa K, Eto M, Kuzuya Y, Hori G, Yamamoto K: Soy protein peptic hydrolysate with bound phospholipids decrease micellar solubility and cholesterol absorption in rats and Caco-2 cells. J Nutr 1999, 129:1725-1730.
• [20]Ong LD, LeClare PC: The Kolmogorov-Smirnov test for the log-normality of sample cumulative frequency distributions. Health Phys 1968, 14:376.
• [21]Rosenthal R: An application of the Kolmogorov-Smirnov test for normality with estimated mean and variance. Psychol Rep 1968, 22:570.
• [22]Snedecor GW, Cochran WG: Statistical methods. In Ames, Japanese Edition: Iwanami Pub. Inc. 6th edition. Tokyo: The Iowa State University Press; 1967.
• [23]Luthi-Peng Q, Märki HP, Hadváry P: Identification of the active-site serine in human pancreatic lipase by chemical modification with tetrahydrolipstatin. FEBS Lett 1992, 299:111-115.
• [24]Filippatos TD, Derdemezis CS, Gazi IF, Nakou ES, Mikhailidis DP, Elisaf MS: Orlistat-associated adverse effects and drug interactions a critical review. Drug Saf 2008, 31:53-65.
• [25]Carrière F, Renou C, Ransac S, Lopez V, de Caro J, Ferrato F, de Caro A, Fleury A, Sanwald DP, Lengsfeld H, Beglinger C, Hadvary P, Verger R, Laugier R: Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers. Am J Physiol Gastrointest Liver Physiol 2001, 281:G16-G28.
• [26]Moreno DA, Ilic N, Poulev A, Raskin I: Effects of Arachis hypogaea nutshell extract on lipid metabolic enzymes and obesity parameters. Life Sci 2006, 78:2797-2803.
• [27]Desmarchelier C, Dahlhoff C, Keller S, Sailer M, Jahreis G, Daniel H: C57Bl/6 N mice on a western diet display reduced intestinal and hepatic cholesterol levels despite a plasma hypercholesterolemia. BMC Genomics 2012, 13:84. BioMed Central Full Text
• [28]Rueda-Clausen CF, Padwal RS, Sharma AM: New pharmacological approaches for obesity management. Nat Rev Endocrinol 2013, 9:467-478.
• [29]Foucault AS, Mathe V, Lafont R, Even P, Dioh W, Veillet S, Tome D, Huneau JF, Hermier D, Boulange AQ: Quinoa extract enriched in 20-hydroxyecdysone protects mice from diet-induced obesity and modulates adipokines expression. Obesity 2012, 20:270-277.
• [30]Ables GP, Perrone CE, Orentreich D, Orentreich N: Methionine-restricted C57BL/6 J mice are resistant to diet-induced obesity and insulin resistance but have low bone density. PLoS One 2012, 7:e51357.
• [31]Takasawa K, Kubota N, Terauchi Y, Kadowaki T: Impact of increased PPARγ activity in adipocytes in vivo on adiposity, insulin sensitivity and the effects of rosiglitazone treatment. Endocr J 2008, 55:767-776.
• [32]Heymsfield SB, Segal KR, Hauptman J, Lucas CP, Boldrin MN, Rissanen A, Wilding JP, Sjöström L: Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med 2000, 160:1321-1326.