LIPID METABOLISM 



I 171 



the lumen. What the stimulus is to cause this pro- 

 liferative (or accumulative) element is unknown; the 

 answer to this question is vital to a proper under- 

 standing of the intimate pathogenesis of athero- 

 sclerosis. 



In summary, the major facts concerning the pa- 

 thology of atherosclerosis, particularly its grosser 

 aspects and its sequelae, are well documented. Debate 

 still exists, however, concerning the more subtle, 

 microscopic manifestations of the early atheroma, 

 particularly in regard to the primacy of lipid deposi- 

 tion. 



After more than fifty years, the lipid theory, despite 

 some unanswered questions, seems to be standing the 

 test of time. It will not become a universally accepted 

 theory until certain difficulties are overcome. The 

 spotty localization of arterial lesions, the mechanism 

 of incorporation of lipid into tissue cells, and the 

 stimulus to cellular accumulation in atheromatous 

 lesions all are unsolved problems. 



METABOLIC CONSEQUENCES OF INGESTION OF FOOD 



rebuilt by the body into new protein. Some of the 

 amino acids can be converted to carbohydrate and 

 thence to fat. Their carbon skeletons also are available 

 for oxidation. 



Following digestion, fatty acids passing through the 

 intestinal mucosa are incorporated into very low- 

 density lipoproteins (chylomicrons); these "mole- 

 cules" are distributed in the systemic circulation to 

 be disposed of by hydrolysis, oxidation, interconver- 

 sion (but not into carbohydrate), or storage in various 

 tissues. 



Thus, carbohydrate and protein can be converted 

 to and stored in the body as fat. 



Soon after a conventional meal has been consumed, 

 changes in concentration of glucose, amino acids, 

 and fat (chylomicrons) occur in the blood. These 

 "primary" changes induce "secondary" changes in 

 the metabolic state. Ingestion of fat is followed by a 

 postprandial lipemia, which may last for many 

 hours. Thus, to evaluate the serum lipids properly, 

 it is important to obtain blood samples from subjects 

 who are in the postabsorptive state. 



Assimilation of foodstuffs is a condition of animal 

 life. Yet food is never deposited unchanged. For 

 absorption to take place, foodstuffs must be split, 

 and far-reaching chemical transformations follow the 

 absorption of digested food. The transformed food 

 may be oxidized for the immediate production of 

 energy or stored for short or long periods, depending 

 on the needs of the body. With the exception of cer- 

 tain essential nutrients, the body is able to synthesize, 

 interconvert, store, and mobilize its constituents. 



When an individual ingests an assimilable carbo- 

 hydrate, practically all of it is absorbed from the 

 digestive tract and eventually reaches the liver as 

 hexose. Part of the hexose is converted to liver glyco- 

 gen; part is released into the circulation to be dis- 

 tributed to extrahepatic tissues; part enters muscle, 

 where it is either burned or stored as glycogen. Once 

 glucose enters muscle, becoming phosphorylated, it 

 can no longer leave as such. One of its breakdown 

 products, lactic acid, can diffuse out of muscle cells 

 and re-enter the circulation. The adipose cells trans- 

 form glucose into fatty acids, which are esterified with 

 a-glycerophosphate to form triglyceride and are 

 stored in this form. Glucose products, by a process of 

 transamination, can be converted into amino acids. 



Protein must be hydrolyzed into amino acids prior 

 to absorption. Subsequently the amino acids can be 



DIET 



The average American diet, according to a sum- 

 mary of the 1 955 Household Food Consumption 

 Survey conducted by the United States Department 

 of Agriculture (65), derives 44 per cent of its caloric 

 content from fat, 1 3 per cent from protein, and 43 

 per cent from carbohydrate. The survey made no 

 deductions for food discarded. The breakdown of 

 calories derived from fat was: 18.3 per cent from satu- 

 rated fatty acids, 18.6 per cent from oleic acid, and 

 4.5 per cent from linoleic acid. As expected from such 

 an extensive survey, there were some regional differ- 

 ences in types and quantities of food consumed. 



Knowledge of the chemical composition of natural 

 fats remains incomplete, although great strides for- 

 ward are being made. It is generally agreed that 

 most natural fats, whether animal or vegetable, con- 

 tain about 98 to 99 per cent triglycerides. The re- 

 maining 1 or 2 per cent includes diglycerides, mono- 

 glycerides, free fatty acids, phospholipids, and 

 unsaponifiable sterols. Fatty acids comprise over go 

 per cent of the triglycerides, with the remainder 

 being glycerol. The naturally occurring triglycerides 

 are mixtures varying widely in their patterns of fatty- 

 acids. The complexity of such glycerides is underlined 



