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This reproduction is the best copy available CONJUGATED LtNOLEIC ACID: ANALYSIS, TISSUE DISTRIBUTION, METABOLISM, AND ITS EFFECTS ON IMMUNE-INDUCED GROWTH DEPRESSION IN RATS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Yiyu Fang, M.S. ****** The Ohio State University 1998 Dissertation Committee: Approved by Professor David B. Min, Adviser Professor Yung-Sheng Huang Professor Ahmed E. Yousef Adviser Professor Tammy M. Bray Food Science and Nutrition Graduate Program UMI Nimber: 9833974 UMI Microform 9833974 Copyright 1998, by UMI Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. UMI 300 North Zeeb Road Ann Arbor, MI 48103 ABSTRACT Conjugated linoleic acid (CLA) has been reported to be a potential nutrient for improving human health. However, detailed information on its effects in animal is not available. This study examed the the effect of dietary CLA on the response of rats to the imminu-induced growth depression caused by endotoxin injection and the posible mechanism involved in the effect. Four week old rats were fed either a 1% linoleic acid (LA) or 1% CLA supplemented diet (30 rats in each dietary group) for 30 days. At day 31 of the experimental diet, 24 rats from each dietary group were injected with 2 mg LPS/kg body weight. Body weight and feed consumption were monitored daily for 7 days after the endotoxin injection. Six rats from uach dietary group were sacrificed at 6, 24, 72, and 144 hour after the endotoxin injection. Plasma, liver, heart, lung, spleen, kidney, muscle and adipose tissue were collected for the lipid content analysis. Plasma prostaglandin 52 (PGE 2) and leukotriene B 4 (LTB4 ) were determined by enzyme immunoassay. The lipid contents of all tissues except heart in the CLA group were less than those in the LA group (p<0.05) while ihe organ weights in both groups were not significantly different. Rats in the CLA group experienced less body weight lose (p<0.05) and more food intake than the LA group after the endotoxin injection. Plasma LTB 4 in CLA group was significantly lower than in the LA group, but PGE 2 in both group were similar. Dietary CLA can effectively reduce lijiid contents of tissues and help to overcome the growth depression due to endotoxin injection. UJ ACKNOWLE DGMENTS I would like to thank my adviser, Dr. David B. Min, for his support, direction, encouragement, and enthusiasm which made this dissertation possible. I would like to thank Dr. Yung-Sheng Huang for his intellectual support, constant encouragement, and his patience in correcting both my stylistic and scientific errors. I also would like to thank the members of my committee. Dr. Ahmed E. Yousef, Dr. Tammy Bray, for their time and useful comments that ed to the improvement of this dissertation. Special thanks is for Dr. Jim Liu and E. Bobik for their ideas, time, and superior technical assistance. I am grateful for t ie financial support received from Ross Laboratory. My sincere appreciation is expressed to rny parents and my husband for their patient and constant support. IV VITA March 23, 1963 ...................................... Bom. Gangzhou, P.R. China June, 1985 ................................................. B.S. Chemistry Department of Chemistry Harbin Institute of Technology Harbin, P. R. China June, 1988 ...................................................M.S. Analytical Chemistry China University of Geosciences Beijing, P.R. China July, 1988 - November, 1991 ................. Research Associate, Department of Chemistry, China University of Geosciences, Beijing, P.R. China August, 1995 ...................................... M.S. Nutrition Department of Food Science & Human Nutrition Iowa State University. January, 1992-July, 1995 .................... Research Assistant, Department of Food Science & Human Nutrition, Iowa State University. October, 1995 - October, 1997 ............ Graduate Research Associate, Department of Food Science & Technology, The Ohio State University. PUBLICATIONS 1. Fang. Y., T.L. Li, D.B. Min, T. Bray, E. Bobik, and Y.S. Huang, Analysis of conjugated linoleic acid (CLA) in animal tissue samples. Abstract for 1997 IFT Annual Meeting, 1997. 2. Fang, Y., D.B. Min, T. Bray, and Y.S. Huang, Effeet of short-term feeding of conjugated linoleic acid (CLA) on fatty acid distribution in rat tissues. Abstract for 88 th ACCS Annual Meeting, 1997. 3. R. Serfass, Y. Fang and M. Wastncy, Zinc kinetics in weaned piglets fed marginal zinc intake: compartmental analysis of stable isotopic data. The Journal o f Trace Elements in Experimental Medicine, 9:73-86, 1996. 4. R. Serfass, Y. Fang and M. Wastncy, Compartmental modeling of stable isotopic zinc metabolism by piglets fed marginal zinc intakes. Abstract for Experimental Biology 95^^^. 5023, 1995. 5. Freeman, S.P.H.T., R E. Serfass, C. King, J R. Southon, Y. Fang, L.R. Woodhouse, G. S. Bench, and J.E. McAninch, Biological sample preparation and '^'Ca AMA measurement at LLNL. Nuclear Instruments and Methods in Physics Restarch, B99:557-561, 1995. 6 . R. E. Serfass, Y. Fang and J. C. King. Preparation of Urinary Calcium for ‘^^Ca/'^^Ca Determination b\" Accelerator Mass Spectrometry i AMS). Abstract for Experimental Biology 9 5 ™ , 4101,1994. FIELDS 01' STUDY Major Field: Food Science and Nutrition VI TABLE OF CONTENTS Page. A bstract ...........................................................................................................................................ii Acknowledgments ........................................................................................................................ vi V ita ..................................................................................................................................................V Publications ....................................................................................................................................vi Table of Contents ........................................................................................................................ vii List of Tables ................................................................................................................................ ix List o f Figures ................................................................................................................................ x Chapters 1. Introduction ............................................................................................................................. l 1.1 Hypothesis ...................................................................................................................... 4 1.2 Objectives ....................................................................................................................... 7 1.3 Significance of this research .......................................................................................... 8 2. Literature Review ..................................................................................................................10 2.1 Conjugated linoleic acid ................................................................................................10 2.1.1 Definition and chemical structures .............................................................. 10 2.1.2 CLA analysis ...................................................................................................11 2.1.3 CLA in food ....................................................................................................13 2.1.4 CLA in biological materials ...........................................................................17 2.1.5 CLA Origin in Animals and Humans ...........................................................20