INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. University Microfilms International A Beil & Howeil Information Company 300 North Zeeb Road. Ann Arbor. Ml 48106-1346 USA 313 761-4700 800 521-0600 Order Number 9238253 Effects of high unsaturated fat diets on low-density lipoprotein receptor activity in freshly isolated human mononuclear cells Park, Sunmin, Ph.D. The Ohio State University, 1992 UMI .HK) N. Zeeh Rd. Ann Arhor. Ml 48106 EFFECTS OF HIGH UNSATURATED FAT DIETS ON LOW DENSITY LIPOPROTEIN RECEPTOR ACTIVITY IN FRESHLY ISOLATED HUMAN MONONUCLEAR CELLS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the Graduate School of The Ohio State University By Sunmin Park, B.S., M.S. >|< # )fc % $ The Ohio State University 1992 Dissertation Committee: Approved by Jean T. Snook Donald Palmquist Adviser Gordon M. Wardlaw Human Ecology Graduate Program Copyright by Sunmin Park 1992 To My parents ACKNOWLEDGEMENT I express my sincere gratitude to my adviser, Dr. Jean T. Snook for constant and patient guidance and assistance throughout the course of my doctoral studies, and for being an example of a deliberate and dedicated professor. Thanks also go to Dr. Donald Palmquist and Dr. Gordon M. Wardlaw for their worthwhile advice and assistance in the preparation of this dissertation. I would like to acknowledge Dr. Silvia McCune, Dr. Robert B. Disilvestero and Dr. Douglas A. Wolfe for serving on my General Examination Committee. I must express my thanks to Dr. Robert J. Nicolosi and Dr. Arthur F. Stucchi at University of Lowell who assisted me in establishing the method to measure LDL receptor activity. Sincere gratitude to Dr. Michael Darby who assisted to iodinate LDL is given. The assistance of Lloyd Mobley and Tim McKnight who drew blood from the subjects, and the'assistance of Myoung Sook Lee, Donna Yount, Victor F. Ferrini and Donna Kinsey is gratefully acknowledged. I also appreciate all subjects in the study for following their diets and encouraging each other. Finally, I must acknowledge my father, Heunggue Park, and my mother, Jungja Lee, for their support and encouragement to continue my doctoral program. VITA 1985 Registered dietician in Korea 1985 B.S., The Ewha Women's University, Seoul Korea 1 9 8 5 -1 9 8 7 Teaching Associate, Department of Food and Nutrition, The Ewha Women's University, Seoul Korea 1987 M.S., The Ewha Women's University, Seoul Korea 1 9 8 7 -1 9 8 8 Researcher, Department of Nutrition, Institution of Food Science and Food Management, Seoul, Korea 1 9 8 9 -1 9 9 1 Research Associate, Department of Human Nutrition and Food Management 1 9 9 1 -1 9 9 2 Anna E. Broden Fellowship, The Ohio State U niversity Member of Kappa Omicron Nu Fields of Study Major Field: Human Ecology Human Nutrition: Dr. Jean T. Snook Dr.Robert B. Disilvestero Nutritional Biochemistry: Dr. Silvia McCune Statistics: Dr. Douglas A. Wolfe TABLE OF CONTENTS ACKNOWLEDGEMENTS.................................................................................... iii VITA ................................................................................................................................iv LIST OF TABLES .............................................................................................. xiii LIST OF FIGURES ......................................................................................... xviii CHAPTER PAGE I. INTRODUCTION .................................................................................................. 1 BACKGROUND ....................................................................................... 1 RESEARCH HYPOTHESIS.................................................................. 4 DEFINITION OF TERM S .................................................................... 6 LIMITATIONS OF STUDY ............................................................... 11 ASSUMPTIONS OF THE STUDY .............................................. 12 II. REVIEW OF THE LITERATURE..................................................... 14 INTRODUCTION................................................................................... 14 STRUCTURE AND FUNCTION OF CHOLESTEROL .... 15 CHOLESTEROL METABOLISM IN THE BODY ................. 17 STRUCTURE AND FUNCTION OF LIPOPROTEINS . 19 METABOLISM OF LIPOPROTEIN S.......................................... 24 A. D igestion ................................................................................. 24 B. Endogenous metabolism ..................................................... 30 C. HDL m etabolism ................................................................. 33 CHARACTERISTICS OF LDL, MODIFIED LDL AND APOPROTEIN B -100 ...................................................................... 36 A. Low density lipoproteins ...................................................... 36 B. Apoprotein B - 1 0 0 .................................................................... 38 C. Modified Lipoproteins ......................................................... 39 STRUCTURE AND FUNCTION OF LDL RECEPTOR . 43 REGULATION OF LDL RECEPTOR ............................................. 53 ATHEROSCLEROSIS............................................................................. 59 INTERACTION OF LDL AND ATHEROSCLEROSIS .... 65 EFFECT OF DIFFERENT FAT DIETS ON LDL RECEPTOR ACTIVITY .............................................................. 67 THE EFFECT OF HORMONES ON THE ACTIVITY OF LDL RECEPTOR .................................................................. 76 A. Thyroid h o rm o n e .................................................................... 76 B. Estrogen ...................................................................................... 77 C. In su lin ............................................................................................ 78 CHANGES OF LDL RECEPTOR ACTIVITY IN DIFFERENT DISEASE STATES .............................................. 79 A. D ia b e te s ....................................................................................... 79 B. O b e sity ........................................................................................... 83 III. EXPERIMENTAL DESIGN/METHOD.........................................................86 INTRODUCTION ..............................................................................................86 vi SUBJECTS 87 RESEARCH DESIGN ............................................................................ 89 DIET P L A N ............................................................................................... 91 ANALYTICAL M EASUREM ENTS.................................................... 95 A. L ipoproteins ...................................................................................95 B. LDL receptor activity .............................................................. 97 C. Fatty acid composition of mononucelar cells . 106 D. Fatty acid composition of meals .................................................107 STATISTICAL ANALYSIS.................................................................... .108 IV. RESEARCH RESULTS...................................................................................... I l l INTRODUCTION.............................................................................................. I l l SUBJECT INFORMATION AND DIET INTAKE .................... 112 A. Subject Information ............................................................... 112 B. Energy expenditure prior to each period . 115 C. Self-selected high butter diet during the one week standardization period before each p e rio d ............................................................................................ 116 D. Dietary intake during both experiment periods and body weight ..................................................................117 E. Summary of characteristics of subjects and dietary intake ............................................................................... 121 THE NORMALITY OF EACH VARIABLES ......................... 123 SERUM LIPID PROFILES ............................................................... 124 A. Serum total cholesterol l e v e ls ..........................................