Observations Concerning the Production and Excretion of Cholesterol in Mammals

The route of absorption of steroids from the gastrointestinal tract seems to l)e largely determinedl bv the chemiiical nature of the comiipounds. AMethyl testosterone (1), 17a-methvl estradiol (2), and cortisone acetate (3) are al)sorl)ed in the rat by way of the portal circulation. Stu(lies fromii this lal)oratory in lhtumiian sul)jects showedI that testosterone, cortisol. cortisone acetate, and corticosterone are also absorbed in this miianner and are virtually absent fromii the lymph (4). In contrast, absorption of cholesterol into lymph of the rat (5,6) and(I dog (7) accounts for essentially all of the sterol that eniters these species fromii the diet. Although it miiight be anticipated fromii these animiial studies and fronm the nonpolar nature of the nmolecule that cholesterol woould be absorbed via the lymiiph in hutmiian subjects, it was of interest to test this directly, since somiie aspects of steroid metabolism in the laboratory animiial are different fromii those observed in miian (8)(9)(10). By miieans of cannulation of the thoracic duct andI the administration of labeled cholesterol. it has been possible for the first tinme to study directlv the absorption and esterification of cholesterol in mlan. These stutlies have demlonistrated that dietary cholesterol is largely absorbed throtugh the lymphatics an(d that the miiajor l)ortion is esterifiedI (luring the absorp)tive parocess. MATERIAL AND METIIODSThe clinical data concerninig the subjects are given in Table I Cholesterol-14, 15-H3 anid sodium acetate-2-C14 were given to 1 subject while cliolesterol-4-C" was adminiistered to 3 other patienits. The raclioactive compoun(ds were giveni orally alnd the amnounits are listed in Table I. Radiochemically pure free ani(l ester clholesterol were isolate(d from l)lasma and(I red cells by methods that have been describe(l (11 ). Free anid ester cholesterol were also obtainied from lymph by the same procedures, but in a few inistanices lymph was dlel)roteinized with acetoniealcohol, the solutioni was concenitrated, anid the l)ortion of the residue that was soluble in petroleum ether was chromatographed oni alumiinla to isolate free clholesterol ani(l cholesterol esters. C 1 radioactivity was (leterminied by coulntinig cholesterol digitoniide mounited oni stainiless steel planchets in a winidowless gas-flow counlter ( 12). C14 activity was also nmeasured by combustioni of clholesterol digitonidle anid couIntinig the carboni dioxide ( 13); tritium was determinied in the same samI)le by reducinig the water pro-(luced by the combustioni to lhydcrogeni anid counltinlg in the proportional regioni ( 14). Figure 1 shows the specific activity of lymph andl l)lasml)a cholesterol-C14 observed over 75 hours following the oral admllinistration of cholesterol-4-C14 to Subject XV.I. The lymph free anid ester chlolesterol attained a peak specific activity at 8 hours. It should be note(l that ester cholesterol appeared promnptly in the lymph although free cholesterol was admiiinistered. The specific activity of the lymph este...

Section: Resultssupporting

confidence: 89%

Section: Resultssupporting

confidence: 78%

Direct Measurement of Cholesterol Absorption via the Thoracic Duct in Man *

Hellman¹,

Frazell²,

Rosenfeld³

1960

“…The ingestion of a ration containing excess cholesterol and cholic acid has been shown to induce chronic hypercholesteremia in rats (6, 7), due to the increased intestinal absorption of cholesterol effected by simultaneous administration of cholate (8). The effect of ingesting this supplemented diet for six days upon the hyperlipemia and hypercholesteremia of nephrotic rats and of the plasma lipids of normal rats is presented in Table II.…”

Section: Resultsmentioning

confidence: 99%

The Role of Exogenous Lipids in the Hyperlipemia and Hypercholesteremia of Nephrotic Rats 1

Friedman¹,

Rosenman²,

Byers³

1954

Self Cite

The renal disease, ascites, subcutaneous edema, and hyperlipemia induced in rats by injection of rabbit anti-rat kidney serum comprise a syndrome which closely resembles the nephrotic state as it occurs in humans (1). This provides a unique opportunity to study the mechanism(s) of the disturbed lipid metabolism of the nephrotic state. In previous studies from this laboratory it was found that the hypercholesteremia of nephrotic rats cannot be ascribed either to an increased intestinal absorption of dietary cholesterol (2) or to an increased hepatic synthesis of endogenous cholesterol (3). In the present study the role of exogenous lipids is further assessed, the data showing that the development of experimental nephrotic hyperlipemia and hypercholesteremia is independent of dietary fat. METHODS AND MATERIALTwenty male rats (Long-Evans strain), were injected intravenously with 0.5 ml. of rabbit anti-rat kidney serum (1) on each of two successive days. Seven of the rats (Group I) were fed a fat and sterol-free ration for five days prior to injection of immune serum, and continued to ingest this ration. Eight rats were fed stock laboratory ration (Group II) and five others (Group III) ingested stock ration supplemented with cholesterol (2 per cent of the diet) and cholic acid (1 per cent of the diet). The cholesterol and cholic acid-supplemented diet also was fed to six normal rats (Group IV) which were not injected with anti-kidney serum. A fifth group of ten other control rats (Group V) were fed stock ration.Each rat was bled from the tail six days after the injection of immune serum, and assay made according to previously described methods of the plasma concentrations of total cholesterol (4) and total lipids (5). Four days later similar determinations again were made in the rats ingesting stock ration (I) and the fat-sterol-free diet (II).X Aided by grants from the American Heart Association and research grant A-46 from the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Public Health Service. RESULTSSix days after the administration of immune serum all of the injected rats exhibited ascites, and lipemic-turbidity of their plasma. Table I presents the averages and ranges of plasma total lipids and total cholesterol values obtained from the nephrotic rats fed stock ration (Group II), those fed the diet free of fats and sterols (Group I), and the normal rats fed stock ration (Group V). The data show that the rats fed the fat-sterol-free diet developed a degree of hyperlipemia and hypercholesteremia equal to, or slightly greater than that developed by the nephrotic animals ingesting stock ration. The nephrotic rats of both groups exhibited a similar degree of ascites, subcutaneous edema, and grossly apparent turbidity of the plasma samples.The ingestion of a ration containing excess cholesterol and cholic acid has been shown to induce chronic hypercholesteremia in rats (6, 7), due to the increased intestinal absorption of cholesterol effected by simultaneous administration of...

“…The experiments of Siperstein, Jayko, Chaikoff, and Dauben (14) indicate that after administration of cholesterol the sustained fecal excretion of radioactivity is chiefly in the form of acidic transformation products, such as bile acids. Animal studies (15,16) show that dietary cholesterol is absorbed within one day and is esterified during the absorptive process. Both the free and esterified sterol pass into the intestinal lymphatics and enter the venous side of the circulation.…”

Section: Absorption and Excretion Of Labeled Cholesterolmentioning

confidence: 99%

Isotopic Studies of Plasma Cholesterol of Endogenous and Exogenous Origins 1

Hellman¹,

Rosenfeld²,

Eidinoff³

et al. 1955

This study was undertaken in order to compare the metabolic behavior of plasma cholesterol de-rived from the diet with that of cholesterol synthesized in vAvo from acetate (1). Cholesterol labeled with either isotopic carbon or hydrogen was administered orally to human subjects and the incorporation into plasma cholesterol was followed over an extended period. In certain instances, both endogenous and exogenous cholesterol metabolism were studied simultaneously by the use of appropriately labeled acetate and cholesterol. These techniques were also applied to an examination of the behavior of plasma cholesterol in four patients with hypercholesterolemia.