CHAPTER 34 



Lipid metabolism in relation to physiology 

 and pathology of atherosclerosis 



SAMI A. HA SHIM 



WILLIAM C . FELCH 



THEODORE B. VAN ITALLIE 



Department of Medicine, St. Luke's Hospital, and Institute of 

 Nutrition Sciences, Columbia University, New York City 



CHAPTER CONTENTS 



Pathology 



Pathogenesis 



Metabolic Consequences of Ingestion of Food 



Diet 



Fat Absorption and Digestion 



Adipose Tissue 



Hormonal Influences on Adipose Tissue 

 The Serum Lipids 



Chylomicrons 



The Lipoproteins 



Free Fatty Acids 



Role of the Liver 



Cholesterol Disposal 

 Factors That Influence Serum Lipids 



Stress 



Sex 



Dietary Fatty Acids 



Essential Fatty Acid (EFA) "Deficiency" 



Chain Length, Unsaturation, and Melting Point 



Dietary Cholesterol 



Practicable Diets 



Mechanism of Cholesterol Lowering 



Additional Influences on Serum Lipids 

 Blood Lipids and Atherosclerosis 

 Role of Blood Clotting and Thrombosis 



the term "lipid" enables us to assemble under one 

 heading a number of organic substances which, 

 although variable in chemical structure, are closely 

 related in biological behavior. The physical and 

 chemical processes by which a living organism oper- 

 ates are summarized bv the term "metabolism." 



Thus, lipid metabolism refers to the behavior in 

 living organisms of fatty acids, their esters, certain 

 hydrocarbons, phospholipids, and sterols. Recent 

 technical advances permitting better separation, 

 identification, and quantification of the various lipids 

 have resulted in a vast store of new information about 

 lipid metabolism. Much of this material still needs 

 to be organized and evaluated in terms of its relevance 

 to problems of human health. 



''Atherosclerosis" (Gr. athero, mush) refers to a 

 lesion of the arterial wall characterized, inter alia, 

 by accumulation of lipid in the intima. The term was 

 first suggested in 1904 by Marchand (144). Today 

 atherosclerosis, by virtue of its deleterious effects on 

 the various arteries of the heart, brain, and other 

 important areas of the body, appears to be the major 

 public health problem of Western man. Thus, by 

 extension, lipid metabolism as it relates to the physi- 

 ology and pathology of blood vessel walls has become 

 a subject of vital importance. 



The search for the etiology of atherosclerosis has 

 included consideration of all elements in the classic 

 epidemiologic triad — agent, host, and environment. 

 Environmental factors have received special attention 

 since evidence — epidemiologic, experimental, and 

 clinical — has accumulated suggesting that dietary 

 constituents and particularly dietary fats influence the 

 development of atherosclerosis. Such evidence as 

 applied to man necessarily has been indirect because 

 of the inaccessibility of atherosclerotic lesions during 

 life. It is now recognized that dietary constituents 

 can profoundly influence lipid metabolism. The role 



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