Studies on the influence of dietary cholesterol on cholesterol metabolism in the isotopic steady state in man.

182

Summary. The absorption of cholesterol has been studied in man by perfusing the upper jejunum with a micellar solution of bile salt, 1-monoglyceride, and cholesterol-14C, with a triple lumen tube with collection sites 50 cm apart. The absorption of micellar components between the collection sites was calculated from their concentration changes relative to those of the watersoluble marker, polyethylene glycol. Control experiments were performed with cholesterol-free perfusions of saline or bile salt-monoglyceride solutions. Steady state conditions were obtained.Each of the components of the micelle was absorbed to a different extent during passage through the test segment of jejunum. Bile salt was not absorbed (mean, -3%), but micellar monoglyceride was rapidly hydrolyzed and absorbed almost completely (mean, 98%). Cholesterol radioactivity was absorbed to an intermediate extent (mean, 73%), and the absorption of chemically determined cholesterol (mean, 46%) indicated that much of the disappearance of radioactivity represented true absorption and not simple exchange.The specific activity of the perfused cholesterol fell during passage through the loop. This fall was interpreted as signifying the continuous addition of nonradioactive endogenous cholesterol by the test segment. However, the decrease in specific activity may also be considered to signify exchange, in that nonradioactive molecules entered the lumen as radioactive molecules were absorbed. Plant sterols appeared in the intestinal contents during the perfusion and must have been contributed by the perfused segment.The perfusate and samples taken from the upper and lower collection sites were examined by ultracentrifugation to define the physical state of cholesterol. It was found that cholesterol in the perfusate or upper collection site samples did not sediment, but that 23% of the cholesterol in the lower collection site samples was sedimentable (mean of three experiments); bile salt, as control, was not sedimentable. Solubility experiments in model systems showed that cholesterol possessed low solubility in bile salt solution; its solubility increased markedly and in linear proportion to the amount of

Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 91%

Absorption of Cholesterol from a Micellar Solution: Intestinal Perfusion Studies in Man*

Simmonds¹,

Hofmann²,

Theodor³

1967

182

“…This observation coned in the accompanying firms earlier work in dogs and rats that led to the conclusion that on cholesterol-rich diets plasma cholesterol a cholesterol-free diet. was derived almost entirely from dietary cholesterol, e have noted in these six and that endogenous cholesterol synthesis was almost er than those previously totally repressed (20)(21)(22)(23).…”

Section: Resultsmentioning

confidence: 86%

Regulation of Cholesterol Metabolism in the Dog

Pertsemlidis¹,

Kirchman²,

Ahrens³

1973

A B S T R A C T Six adult pedigreed dogs were studied as long as 3 yr in order to determine the effects of cholesterol feeding and of bile diversion on absorption, synthesis, and storage of cholesterol. These measurements were based on cholesterol balance and isotope kinetic studies.In the six dogs fed a "cholesterol-free" diet with their enterohepatic circulations undisturbed, the rate of cholesterol synthesis ranged from 225 to 508 mg/day (mean 325 mg/day or 12.4 mg/kg/day). In two dogs studied subsequently on cholesterol-containing diets, absorption of cholesterol averaged 81% (range 71-94%) on a dietary intake of 0.5 g/day; on high cholesterol intakes (2.7-3.0 g/day) the rate of absorption dropped to 43-51% of daily intake, but the absolute amounts absorbed were increased. Feeding of cholesterol resulted in acceleration of bile acid formation and excretion, as well as nearly total inhibition of cholesterol synthesis. These two compensatory mechanisms were sufficient to maintain zero balance of cholesterol in the face of a high cholesterol intake. Plasma cholesterol concentrations in the two dogs increased by 37 and 44%.In two other dogs bile was completely diverted into the urinary system for nearly 2 yr. When these dogs were studied on a cholesterol-free diet, the sum of acidic steroids excreted daily in urine plus neutral steroids excreted in feces was seven times as high as before the operation. Since these massive excretory losses could not Dr. Pertsemlidis and Dr. Kirchman's present address is

“…This assumption seems reasonable since there is probably only a quantitatively unimportant amount of cholesterol degradation and excretion directly via the peripheral tissue and organ pools which comprise pool B. The known quantitatively important pathways of cholesterol metabolism include the catabolism of cholesterol to bile acids in the liver and the excretion of acidic steroids and neutral sterols via the feces (7,(31)(32)(33). The fecal sterols and sterol metabolites originate mainly in the liver and also partly in the intestinal mucosa.…”

Section: Discussionmentioning

confidence: 99%

Turnover of plasma cholesterol in man

Goodman¹,

Noble²

1968

285

118

A B S T R A C T Cholesterol4-'C was injected intravenously into a series of normal men, untreated hyperlipidemic patients, and hyperlipidemic patients being treated with cholestyramine. The specific radioactivity of plasma total cholesterol was measured during the ensuing 10 wk. 16 studies were carried out in 10 subjects. Analysis of the turnover curves of plasma cholesterol revealed that in every study the turnover of plasma cholesterol conformed to a two-pool model. Each turnover curve was analyzed in terms of this model, as expressed by the equation: specific activity = CAe-at + CBeA0. The parameters which were calculated included the constants CA, CB, a, and 8; the size of the first pool (MA); the rate constants for the total rate of removal of cholesterol from each pool (kA and kBB); and the production rate in pool A (PRA). In two normal men and five untreated patients the average size of pool A-was 25 g.The effect of cholestyramine was assessed by comparing the results obtained without therapy with those obtained during therapy in five subjects studied under both conditions. Cholestyramine therapy produced a large increase in PRA (from 0.98 to 1.98 g/day) and in the rate of removal of cholesterol from pool A. Cholestyramine did not significantly alter the size of pool A.It is not possible to calculate the size of the total body exchangeable pool of cholesterol from the turnover curve of plasma cholesterol. It is also not possible to calculate the metabolic turnover rate,